Colorectal Neoplasms
Conditions
Keywords
GI neoplasms (phase 1)
Brief summary
To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer.
Interventions
DRUGbevacizumab
bevacizumab 5 mg/kg every 2 weeks
DRUGAG-013726
AG-013726 5 mg bid every 2 weeks
AG-013736 5 mg bid starting dose
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment * (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy. * Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was \> 12 months prior to enrollment, * Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication.
Exclusion criteria
* Prior system therapy for advanced CRC (Ph 2 portion only) * Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors. * Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%) * Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed \> 2 weeks of enrollment and be fully recovered from any procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response: Phase 2 | Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) | Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as \>=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUC (t - ∞\] for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose. |
| Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3.Cmax for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose. |
| Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | — |
| Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. CL/F for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. |
| Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. t1/2 for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUClast for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose. |
| Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. Cmax for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose. |
| Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | — |
| Clearance (CL) For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. CL for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. t1/2 for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUClast for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose. |
| Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. Cmax for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose. |
| Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | — |
| Clearance (CL) For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. CL for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. t1/2 for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pharmacokinetic (PK) parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUClast for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose. |
| Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Cmax for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose. |
| Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | — |
| Clearance (CL) For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. t1/2 for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUClast for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose. |
| Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. Cmax for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose. |
| Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | — |
| Clearance (CL) For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. CL for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1 | Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. t1/2 for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. |
| Duration of Response (DR): Phase 2 | Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) | Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR: disappearance of all lesions and no appearance of new lesions. PR: \>=30% decrease in sum of LD of target lesions taking as reference the baseline sum LD, without progression of nontarget lesions and no appearance of new lesions. Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation. |
| Progression-Free Survival (PFS): Phase 2 | Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) | Time in days from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death). Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation. |
| Time to Treatment Failure (TTF): Phase 2 | Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) | TTF is defined as the time from the randomization to the date of the first documentation of PD, symptomatic deterioration, death due to any cause, or treatment discontinuation due to adverse event, refusal or other reasons. Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation. |
| Overall Survival (OS): Phase 2 | Every 3 months after discontinuation of study treatment until death due to any cause or 1 year after randomization of the last participant | Time in days from randomization date to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). |
| Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Cycle 1 Day 1 (baseline), every 2 weeks for the first 2 months (Cycle 2 Day 1 [C2D1], Cycle 3 Day 1, and Cycle 4 Day 1) then monthly thereafter starting Cycle 6 Day 1, and 28 days after the last dose | PROs included assessment of symptom severity and interference which were measured using M.D. Anderson Symptom Assessment Inventory-Diarrhea (MDASI-D), 20-item questionnaire which assesses the severity of 14 symptoms over the past 24 hours, as well as symptoms interference with 6 areas of function (e.g., walking, work, mood), when the symptom was at its worst. Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was as bad as you can imagine or interfered completely with their life. The 2 subscales, symptom severity score and symptom interference score were average of respective items and ranged from 0 to 10, higher score indicating greater severity or interference of symptoms. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1 | Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). AUClast for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1) Bevacizumab 1 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 6 |
| Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2) Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 6 |
| Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3) Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 4 |
| Phase 1: Axitinib + FOLFIRI (Cohort 4) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m\^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to irinotecan infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 8 |
| Phase 1: Axitinib + FOLFOX (Cohort 5) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 6 |
| Phase 1: Axitinib + FOLFIRI (Cohort 6) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m\^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 4 |
| Phase 1: Axitinib + FOLFOX (Cohort 7) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 6 |
| Phase 1: Axitinib + FOLFIRI (Cohort 8) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m\^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 7 mg to 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 3 |
| Phase 1: Axitinib + FOLFIRI (Cohort 9) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m\^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 18 |
| Phase 2: Axitinib + FOLFOX FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 42 |
| Phase 2: Bevacizumab + FOLFOX Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 43 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m\^2 intravenous infusion over 2 hours, leucovorin 400 mg/m\^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m\^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m\^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion. | 41 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 | Adverse Event | 3 | 1 | 1 | 2 | 0 | 0 | 3 | 0 | 4 | 0 | 0 | 0 |
| Phase 1 | Death | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Phase 1 | Lack of Efficacy | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 11 | 0 | 0 | 0 |
| Phase 1 | Other | 0 | 3 | 1 | 1 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Phase 1 | Withdrawal by Subject | 1 | 2 | 1 | 1 | 3 | 0 | 1 | 0 | 2 | 0 | 0 | 0 |
| Phase 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 9 | 10 |
| Phase 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 2 |
| Phase 2 | Global Deterioration of Health Status | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Phase 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase 2 | Objective Progression or Relapse | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 10 | 17 |
| Phase 2 | Ongoing in study A4061008 (NCT00828919) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase 2 | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 16 | 7 |
| Phase 2 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Phase 2 | Randomized, but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| Phase 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 4 | 5 |
Baseline characteristics
| Characteristic | Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1) | Total | Phase 2: Axitinib + Bevacizumab + FOLFOX | Phase 2: Bevacizumab + FOLFOX | Phase 2: Axitinib + FOLFOX | Phase 1: Axitinib + FOLFIRI (Cohort 9) | Phase 1: Axitinib + FOLFIRI (Cohort 8) | Phase 1: Axitinib + FOLFOX (Cohort 7) | Phase 1: Axitinib + FOLFIRI (Cohort 6) | Phase 1: Axitinib + FOLFOX (Cohort 5) | Phase 1: Axitinib + FOLFIRI (Cohort 4) | Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3) | Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 1 Participants | 21 Participants | 8 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Customized 45 to 64 years | 2 Participants | 96 Participants | 23 Participants | 18 Participants | 22 Participants | 13 Participants | 3 Participants | 5 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 3 Participants | 70 Participants | 10 Participants | 21 Participants | 18 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 3 Participants |
| Age, Customized Less than (<) 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 67 Participants | 15 Participants | 15 Participants | 17 Participants | 7 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 120 Participants | 26 Participants | 28 Participants | 25 Participants | 11 Participants | 3 Participants | 4 Participants | 2 Participants | 5 Participants | 6 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 4 / 4 | 8 / 8 | 6 / 6 | 4 / 4 | 6 / 6 | 3 / 3 | 18 / 18 | 39 / 39 | 42 / 43 | 39 / 41 |
| serious Total, serious adverse events | 3 / 6 | 2 / 6 | 2 / 4 | 3 / 8 | 5 / 6 | 1 / 4 | 1 / 6 | 1 / 3 | 8 / 18 | 15 / 39 | 17 / 43 | 23 / 41 |
Outcome results
Primary
Percentage of Participants With Objective Response: Phase 2
Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as \>=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
Time frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
Population: Intent-to-treat (ITT) population included all randomized participants, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: Axitinib + FOLFOX | Percentage of Participants With Objective Response: Phase 2 | 28.6 Percentage of participants |
| Phase 2: Bevacizumab + FOLFOX | Percentage of Participants With Objective Response: Phase 2 | 48.8 Percentage of participants |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Percentage of Participants With Objective Response: Phase 2 | 39.0 Percentage of participants |
Comparison: One-sided Cochran-Mantel-Haenszel test of treatment stratified by prior adjuvant chemotherapy (yes versus \[vs.\] no) and prior pelvic irradiation (yes vs. no) was used for the analysis.p-value: 0.972695% CI: [0.332, 1.031]Cochran-Mantel-Haenszel
Comparison: One-sided Cochran-Mantel-Haenszel test of treatment stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no) was used for the analysis.p-value: 0.839195% CI: [0.399, 1.352]Cochran-Mantel-Haenszel
Comparison: One-sided Cochran-Mantel-Haenszel test of treatment stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no) was used for the analysis.p-value: 0.819295% CI: [0.489, 1.299]Cochran-Mantel-Haenszel
Secondary
Apparent Oral Clearance (CL/F) For Axitinib: Phase 1
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. CL/F for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 1 Day 8 | 30.01 Liter per hour (L/hr) |
| Phase 2: Axitinib + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 2 Day 1 | 30.08 Liter per hour (L/hr) |
| Phase 2: Bevacizumab + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 1 Day 8 | 47.10 Liter per hour (L/hr) |
| Phase 2: Bevacizumab + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 2 Day 1 | 33.33 Liter per hour (L/hr) |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 1 Day 8 | 28.49 Liter per hour (L/hr) |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Apparent Oral Clearance (CL/F) For Axitinib: Phase 1 | Cycle 2 Day 1 | 28.90 Liter per hour (L/hr) |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUClast for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 39212.03 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 45087.71 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 40955.29 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 36533.84 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 52164.28 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 95123.13 ng*hr/mL |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pharmacokinetic (PK) parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUClast for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.
Time frame: Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 1 Day 8 | 119.02 nanogram hour per milliliter (ng*hr/mL) |
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 2 Day 1 | 95.70 nanogram hour per milliliter (ng*hr/mL) |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 1 Day 8 | 106.76 nanogram hour per milliliter (ng*hr/mL) |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 2 Day 1 | 143.68 nanogram hour per milliliter (ng*hr/mL) |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 1 Day 8 | 97.05 nanogram hour per milliliter (ng*hr/mL) |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1 | Cycle 2 Day 1 | 117.47 nanogram hour per milliliter (ng*hr/mL) |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUClast for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1 | Cycle 1 Day 1 | 3394758.83 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1 | Cycle 2 Day 1 | 3554899.52 ng*hr/mL |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). AUClast for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1 | Cycle 1 Day 1 | 12081.58 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1 | Cycle 2 Day 1 | 11496.32 ng*hr/mL |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUClast for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 4814.87 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 5231.71 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 4308.71 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 5303.66 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 36314.14 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 38983.80 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 41460.50 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 36776.79 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 52430.15 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 96632.41 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUC (t - ∞\] for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 1 Day 8 | 190.51 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 2 Day 1 | 224.46 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 1 Day 8 | 113.20 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 2 Day 1 | 168.07 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 1 Day 8 | 205.41 ng*hr/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1 | Cycle 2 Day 1 | 178.46 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1 | Cycle 1 Day 1 | 4987528.96 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1 | Cycle 2 Day 1 | 5114888.84 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1 | Cycle 1 Day 1 | 13055.88 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1 | Cycle 2 Day 1 | 12459.89 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 5955.70 ng*hr/mL |
| Phase 2: Axitinib + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 6744.06 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 5137.31 ng*hr/mL |
| Phase 2: Bevacizumab + FOLFOX | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 6430.67 ng*hr/mL |
Secondary
Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2
PROs included assessment of symptom severity and interference which were measured using M.D. Anderson Symptom Assessment Inventory-Diarrhea (MDASI-D), 20-item questionnaire which assesses the severity of 14 symptoms over the past 24 hours, as well as symptoms interference with 6 areas of function (e.g., walking, work, mood), when the symptom was at its worst. Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was as bad as you can imagine or interfered completely with their life. The 2 subscales, symptom severity score and symptom interference score were average of respective items and ranged from 0 to 10, higher score indicating greater severity or interference of symptoms.
Time frame: Cycle 1 Day 1 (baseline), every 2 weeks for the first 2 months (Cycle 2 Day 1 [C2D1], Cycle 3 Day 1, and Cycle 4 Day 1) then monthly thereafter starting Cycle 6 Day 1, and 28 days after the last dose
Population: ITT population included all randomized participants, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C23D1 (n=4,5,3) | 0.21 units on scale | Standard Deviation 0.42 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C36D1 (n=2,3,2) | 0.29 units on scale | Standard Deviation 0.51 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C3D1 (n=32,38,32) | 0.68 units on scale | Standard Deviation 1.29 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C22D1 (n=3,11,8) | 0.44 units on scale | Standard Deviation 0.84 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C37D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C18D1 (n=6,14,9) | 0.02 units on scale | Standard Deviation 0.85 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C21D1 (n=4,5,5) | -0.04 units on scale | Standard Deviation 0.86 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C38D1 (n=2,2,1) | 0.13 units on scale | Standard Deviation 0.28 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C38D1 (n=2,2,1) | 0.08 units on scale | Standard Deviation 0.12 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C20D1 (n=5,14,8) | 0.27 units on scale | Standard Deviation 0.65 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C39D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C19D1 (n=4,8,6) | 0.04 units on scale | Standard Deviation 0.34 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C18D1 (n=6,14,9) | 0.06 units on scale | Standard Deviation 0.34 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C40D1 (n=2,2,2) | 0.18 units on scale | Standard Deviation 0.35 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C2D1 (n=37,37,37) | 0.63 units on scale | Standard Deviation 1.22 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C17D1 (n=5,11,6) | -0.90 units on scale | Standard Deviation 1.31 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C42D1 (n=2,2,1) | 0.18 units on scale | Standard Deviation 0.35 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C19D1 (n=4,8,16) | -0.18 units on scale | Standard Deviation 0.54 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C16D1 (n=7,17,14) | -0.02 units on scale | Standard Deviation 0.33 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Follow_Up (n=4,15,14) | 1.29 units on scale | Standard Deviation 2.75 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C12D1 (n=11,23,16) | 0.32 units on scale | Standard Deviation 1.4 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C15D1 (n=7,11,9) | -0.52 units on scale | Standard Deviation 0.85 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Baseline (n=41,43,40) | 2.50 units on scale | Standard Deviation 2.7 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Baseline (n=41,43,40) | 1.62 units on scale | Standard Deviation 1.57 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C14D1 (n=8,17,14) | -0.10 units on scale | Standard Deviation 0.84 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C2D1 (n=37,37,36) | 0.46 units on scale | Standard Deviation 1.8 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C20D1 (n=5,14,8) | -0.06 units on scale | Standard Deviation 0.54 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C13D1 (n=8,13,12) | -0.50 units on scale | Standard Deviation 1.56 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C3D1 (n=31,38,30) | 0.60 units on scale | Standard Deviation 2.37 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C40D1 (n=2,2,2) | 0.42 units on scale | Standard Deviation 0.59 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C12D1 (n=10,23,16) | 0.03 units on scale | Standard Deviation 0.78 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C4D1 (n=23,36,30) | 0.92 units on scale | Standard Deviation 2.16 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Follow Up (n=4,15,14) | 1.33 units on scale | Standard Deviation 2.48 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C11D1 (n=10,20,19) | 0.42 units on scale | Standard Deviation 1.23 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C5D1 (n=23,34,29) | 0.65 units on scale | Standard Deviation 2.2 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C21D1 (n=4,5,5) | -0.25 units on scale | Standard Deviation 0.71 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C10D1 (n=14,27,21) | -0.18 units on scale | Standard Deviation 1.8 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C6D1 (n=15,38,26) | 0.32 units on scale | Standard Deviation 2.01 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C8D1 (n=17,29,22) | 0.28 units on scale | Standard Deviation 1.45 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C9D1 (n=11,24,21) | -0.14 units on scale | Standard Deviation 1.08 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C7D1 (n=12,30,22) | 0.43 units on scale | Standard Deviation 1.25 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C37D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C8D1 (n=17,29,22) | 0.01 units on scale | Standard Deviation 1.58 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C22D1 (n=3,11,8) | 0.57 units on scale | Standard Deviation 0.45 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C13D1 (n=8,13,12) | -0.09 units on scale | Standard Deviation 1.43 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C36D1 (n=2,3,2) | 0.17 units on scale | Standard Deviation 0.24 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C23D1 (n=4,5,3) | 0.30 units on scale | Standard Deviation 0.8 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C10D1 (n=14,27,21) | 0.28 units on scale | Standard Deviation 1.37 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C35D1 (n=0,0,1) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C24D1 (n=5,11,7) | 0.91 units on scale | Standard Deviation 2.07 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C7D1 (n=12,30,22) | 0.28 units on scale | Standard Deviation 1.51 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C34D1 (n=2,4,3) | 0.17 units on scale | Standard Deviation 0.24 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C25D1 (n=4,5,5) | 0.25 units on scale | Standard Deviation 0.96 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C14D1 (n=8,17,14) | 0.03 units on scale | Standard Deviation 0.81 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C33D1 (n=0,0,2) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C26D1 (n=4,6,7) | -0.05 units on scale | Standard Deviation 0.76 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C9D1 (n=11,24,21) | -0.15 units on scale | Standard Deviation 1.55 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C32D1 (n=2,4,4) | 0.08 units on scale | Standard Deviation 0.12 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C27D1 (n=4,3,4) | -0.21 units on scale | Standard Deviation 0.65 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C6D1 (n=15,38,26) | 0.70 units on scale | Standard Deviation 1.8 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C31D1 (n=1,1,3) | 0.00 units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C28D1 (n=4,5,7) | 0.12 units on scale | Standard Deviation 0.82 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C15D1 (n=7,11,9) | 0.28 units on scale | Standard Deviation 1.5 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C30D1 (n=3,6,3) | 0.94 units on scale | Standard Deviation 1.49 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C29D1 (n=2,3,4) | 3.00 units on scale | Standard Deviation 2.12 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C39D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C29D1 (n=2,3,4) | 3.25 units on scale | Standard Deviation 3.89 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C30D1 (n=3,6,3) | 1.05 units on scale | Standard Deviation 1.7 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C5D1 (n=23,34,29) | 0.72 units on scale | Standard Deviation 1.37 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C28D1 (n=4,5,7) | 0.71 units on scale | Standard Deviation 1.19 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C31D1 (n=1,1,3) | -0.50 units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C16D1 (n=7,17,14) | -0.30 units on scale | Standard Deviation 0.88 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C27D1 (n=4,3,4) | 0.04 units on scale | Standard Deviation 0.52 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C32D1 (n=2,4,4) | 0.11 units on scale | Standard Deviation 0.25 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C11D1 (n=10,20,19) | 0.15 units on scale | Standard Deviation 1.57 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C26D1 (n=4,6,7) | 0.33 units on scale | Standard Deviation 0.85 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C33D1 (n=0,0,2) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C4D1 (n=23,37,30) | 0.88 units on scale | Standard Deviation 1.41 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C25D1 (n=4,5,5) | 0.00 units on scale | Standard Deviation 0.41 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C34D1 (n=2,4,3) | 0.04 units on scale | Standard Deviation 0.15 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C17D1 (n=5,11,6) | -0.20 units on scale | Standard Deviation 0.7 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C24D1 (n=5,11,7) | 2.00 units on scale | Standard Deviation 3.25 |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C35D1 (n=0,0,1) | NA units on scale | — |
| Phase 2: Axitinib + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C42D1 (n=2,2,1) | 0.25 units on scale | Standard Deviation 0.35 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C39D1 (n=0,1,0) | 0.86 units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C40D1 (n=2,2,2) | 2.50 units on scale | Standard Deviation 2.12 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C42D1 (n=2,2,1) | 2.58 units on scale | Standard Deviation 2.24 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C9D1 (n=11,24,21) | -0.03 units on scale | Standard Deviation 1.67 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C10D1 (n=14,27,21) | 0.06 units on scale | Standard Deviation 1.52 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C11D1 (n=10,20,19) | -0.05 units on scale | Standard Deviation 1.59 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C12D1 (n=11,23,16) | 0.47 units on scale | Standard Deviation 1.37 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C13D1 (n=8,13,12) | 0.10 units on scale | Standard Deviation 1.35 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C14D1 (n=8,17,14) | 0.38 units on scale | Standard Deviation 1.48 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C15D1 (n=7,11,9) | 0.42 units on scale | Standard Deviation 1.49 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C16D1 (n=7,17,14) | 0.11 units on scale | Standard Deviation 1.46 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C17D1 (n=5,11,6) | 0.21 units on scale | Standard Deviation 1.69 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C18D1 (n=6,14,9) | 0.31 units on scale | Standard Deviation 1.15 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C19D1 (n=4,8,16) | 0.34 units on scale | Standard Deviation 1.42 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C20D1 (n=5,14,8) | 0.15 units on scale | Standard Deviation 1.21 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C21D1 (n=4,5,5) | 0.27 units on scale | Standard Deviation 1.9 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C22D1 (n=3,11,8) | 0.81 units on scale | Standard Deviation 0.95 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C23D1 (n=4,5,3) | 0.64 units on scale | Standard Deviation 1.32 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C24D1 (n=5,11,7) | 0.37 units on scale | Standard Deviation 1.1 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C25D1 (n=4,5,5) | -0.03 units on scale | Standard Deviation 1.12 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C26D1 (n=4,6,7) | 0.46 units on scale | Standard Deviation 0.72 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C27D1 (n=4,3,4) | 0.07 units on scale | Standard Deviation 0.99 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C28D1 (n=4,5,7) | 0.74 units on scale | Standard Deviation 1.01 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C29D1 (n=2,3,4) | -0.14 units on scale | Standard Deviation 0.58 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C30D1 (n=3,6,3) | 0.45 units on scale | Standard Deviation 1.05 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C31D1 (n=1,1,3) | -0.64 units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C32D1 (n=2,4,4) | 0.80 units on scale | Standard Deviation 0.93 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C33D1 (n=0,0,2) | NA units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C34D1 (n=2,4,3) | 0.75 units on scale | Standard Deviation 0.89 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C35D1 (n=0,0,1) | NA units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C36D1 (n=2,3,2) | 1.24 units on scale | Standard Deviation 1.22 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C37D1 (n=0,1,0) | 0.86 units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C38D1 (n=2,2,1) | 1.68 units on scale | Standard Deviation 1.97 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C40D1 (n=2,2,2) | 1.29 units on scale | Standard Deviation 1.11 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C42D1 (n=2,2,1) | 1.25 units on scale | Standard Deviation 1.26 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Follow_Up (n=4,15,14) | -0.00 units on scale | Standard Deviation 1.66 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Baseline (n=41,43,40) | 2.79 units on scale | Standard Deviation 2.57 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C2D1 (n=37,37,36) | -0.08 units on scale | Standard Deviation 1.74 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C3D1 (n=31,38,30) | -0.57 units on scale | Standard Deviation 1.88 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C4D1 (n=23,36,30) | -0.54 units on scale | Standard Deviation 1.89 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C5D1 (n=23,34,29) | -0.59 units on scale | Standard Deviation 1.98 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C6D1 (n=15,38,26) | -0.18 units on scale | Standard Deviation 2.33 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C7D1 (n=12,30,22) | -0.59 units on scale | Standard Deviation 2.13 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C8D1 (n=17,29,22) | -0.10 units on scale | Standard Deviation 2 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C9D1 (n=11,24,21) | -0.39 units on scale | Standard Deviation 2.31 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C10D1 (n=14,27,21) | 0.15 units on scale | Standard Deviation 2.06 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C11D1 (n=10,20,19) | -0.51 units on scale | Standard Deviation 1.75 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C12D1 (n=10,23,16) | 0.17 units on scale | Standard Deviation 2.23 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C13D1 (n=8,13,12) | -0.31 units on scale | Standard Deviation 2.49 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C14D1 (n=8,17,14) | 0.15 units on scale | Standard Deviation 2.57 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C15D1 (n=7,11,9) | 0.27 units on scale | Standard Deviation 1.91 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C16D1 (n=7,17,14) | -0.48 units on scale | Standard Deviation 2.31 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C17D1 (n=5,11,6) | -0.29 units on scale | Standard Deviation 3.16 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C18D1 (n=6,14,9) | 0.04 units on scale | Standard Deviation 2.38 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C19D1 (n=4,8,6) | 0.54 units on scale | Standard Deviation 2.25 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C20D1 (n=5,14,8) | -0.08 units on scale | Standard Deviation 2.34 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C21D1 (n=4,5,5) | -0.97 units on scale | Standard Deviation 3.5 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C22D1 (n=3,11,8) | 0.74 units on scale | Standard Deviation 1.71 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C23D1 (n=4,5,3) | 1.13 units on scale | Standard Deviation 2.58 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C24D1 (n=5,11,7) | 0.30 units on scale | Standard Deviation 2.65 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C25D1 (n=4,5,5) | 0.10 units on scale | Standard Deviation 2.45 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C26D1 (n=4,6,7) | 0.67 units on scale | Standard Deviation 1.8 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C27D1 (n=4,3,4) | 0.11 units on scale | Standard Deviation 1.13 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C28D1 (n=4,5,7) | 0.97 units on scale | Standard Deviation 1.81 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C29D1 (n=2,3,4) | -0.56 units on scale | Standard Deviation 0.96 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C30D1 (n=3,6,3) | 1.08 units on scale | Standard Deviation 2.16 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C31D1 (n=1,1,3) | -0.17 units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C32D1 (n=2,4,4) | 1.50 units on scale | Standard Deviation 2.26 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C33D1 (n=0,0,2) | NA units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C34D1 (n=2,4,3) | 1.25 units on scale | Standard Deviation 1.89 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C35D1 (n=0,0,1) | NA units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C36D1 (n=2,3,2) | 1.89 units on scale | Standard Deviation 2.18 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Baseline (n=41,43,40) | 2.20 units on scale | Standard Deviation 1.93 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C2D1 (n=37,37,37) | 0.04 units on scale | Standard Deviation 1.16 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C3D1 (n=32,38,32) | -0.22 units on scale | Standard Deviation 1.17 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C4D1 (n=23,37,30) | -0.40 units on scale | Standard Deviation 1.27 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C5D1 (n=23,34,29) | -0.34 units on scale | Standard Deviation 1.59 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C6D1 (n=15,38,26) | 0.09 units on scale | Standard Deviation 1.44 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C7D1 (n=12,30,22) | -0.16 units on scale | Standard Deviation 1.55 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C8D1 (n=17,29,22) | -0.13 units on scale | Standard Deviation 1.56 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C37D1 (n=0,1,0) | 0.83 units on scale | — |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Follow Up (n=4,15,14) | -0.21 units on scale | Standard Deviation 2.44 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C38D1 (n=2,2,1) | 2.25 units on scale | Standard Deviation 2.47 |
| Phase 2: Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C39D1 (n=0,1,0) | 0.50 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C21D1 (n=4,5,5) | 1.83 units on scale | Standard Deviation 1.28 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C36D1 (n=2,3,2) | -0.18 units on scale | Standard Deviation 0.25 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C3D1 (n=32,38,32) | 0.63 units on scale | Standard Deviation 1.61 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C22D1 (n=3,11,8) | 0.83 units on scale | Standard Deviation 2.05 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C35D1 (n=0,0,1) | 0.79 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C16D1 (n=7,17,14) | 0.05 units on scale | Standard Deviation 2.08 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C23D1 (n=4,5,3) | 1.28 units on scale | Standard Deviation 1.8 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C34D1 (n=2,4,3) | 0.43 units on scale | Standard Deviation 0.74 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Follow Up (n=4,15,14) | 0.91 units on scale | Standard Deviation 1.65 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C24D1 (n=5,11,7) | 0.55 units on scale | Standard Deviation 2.33 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C33D1 (n=0,0,2) | 0.89 units on scale | Standard Deviation 1.26 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C4D1 (n=23,37,30) | 0.64 units on scale | Standard Deviation 1.68 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C25D1 (n=4,5,5) | 0.90 units on scale | Standard Deviation 0.88 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C32D1 (n=2,4,4) | 1.29 units on scale | Standard Deviation 1.03 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C15D1 (n=7,11,9) | 0.71 units on scale | Standard Deviation 1.34 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C26D1 (n=4,6,7) | 0.33 units on scale | Standard Deviation 2.11 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C31D1 (n=1,1,3) | 1.55 units on scale | Standard Deviation 1.69 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C37D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C27D1 (n=4,3,4) | 1.63 units on scale | Standard Deviation 2.44 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C30D1 (n=3,6,3) | 0.64 units on scale | Standard Deviation 0.68 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C5D1 (n=23,34,29) | 0.60 units on scale | Standard Deviation 2.13 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C28D1 (n=4,5,7) | 0.19 units on scale | Standard Deviation 2.4 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C29D1 (n=2,3,4) | -0.09 units on scale | Standard Deviation 2.51 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C14D1 (n=8,17,14) | -0.05 units on scale | Standard Deviation 1.44 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C29D1 (n=2,3,4) | 1.33 units on scale | Standard Deviation 2.97 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C28D1 (n=4,5,7) | -0.43 units on scale | Standard Deviation 2 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C11D1 (n=10,20,19) | 0.57 units on scale | Standard Deviation 1.33 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C30D1 (n=3,6,3) | 1.06 units on scale | Standard Deviation 1.83 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C27D1 (n=4,3,4) | 0.34 units on scale | Standard Deviation 2.7 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C6D1 (n=15,38,26) | 0.96 units on scale | Standard Deviation 1.6 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C31D1 (n=1,1,3) | 2.33 units on scale | Standard Deviation 2.08 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C26D1 (n=4,6,7) | -0.13 units on scale | Standard Deviation 1.79 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C13D1 (n=8,13,12) | 0.73 units on scale | Standard Deviation 1.55 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C32D1 (n=2,4,4) | 2.17 units on scale | Standard Deviation 1.81 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C25D1 (n=4,5,5) | -0.30 units on scale | Standard Deviation 1.63 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C39D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C33D1 (n=0,0,2) | 1.92 units on scale | Standard Deviation 2.71 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C24D1 (n=5,11,7) | -0.20 units on scale | Standard Deviation 1.62 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C7D1 (n=12,30,22) | 0.26 units on scale | Standard Deviation 1.22 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C34D1 (n=2,4,3) | 1.11 units on scale | Standard Deviation 1.51 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C23D1 (n=4,5,3) | 1.05 units on scale | Standard Deviation 1.11 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C12D1 (n=11,23,16) | 0.38 units on scale | Standard Deviation 1.14 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C35D1 (n=0,0,1) | 1.67 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C7D1 (n=12,30,22) | 0.55 units on scale | Standard Deviation 2.05 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C22D1 (n=3,11,8) | 0.09 units on scale | Standard Deviation 1.37 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C8D1 (n=17,29,22) | 0.48 units on scale | Standard Deviation 1.87 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C6D1 (n=15,38,26) | 0.99 units on scale | Standard Deviation 2.54 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C38D1 (n=2,2,1) | -0.17 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C9D1 (n=11,24,21) | 0.75 units on scale | Standard Deviation 1.76 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C5D1 (n=23,34,29) | 1.19 units on scale | Standard Deviation 2.9 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C42D1 (n=2,2,1) | 0.00 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C10D1 (n=14,27,21) | 0.99 units on scale | Standard Deviation 2.12 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C4D1 (n=23,36,30) | 1.15 units on scale | Standard Deviation 2.37 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C36D1 (n=2,3,2) | 1.33 units on scale | Standard Deviation 1.89 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C11D1 (n=10,20,19) | 0.84 units on scale | Standard Deviation 2.5 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C3D1 (n=31,38,30) | 1.09 units on scale | Standard Deviation 2.37 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C21D1 (n=4,5,5) | 1.20 units on scale | Standard Deviation 1.35 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C12D1 (n=10,23,16) | 0.38 units on scale | Standard Deviation 1.51 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C2D1 (n=37,37,36) | 0.78 units on scale | Standard Deviation 2.55 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C20D1 (n=5,14,8) | -0.06 units on scale | Standard Deviation 1.67 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C13D1 (n=8,13,12) | 0.31 units on scale | Standard Deviation 1.7 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: Baseline (n=41,43,40) | 2.47 units on scale | Standard Deviation 2.66 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C19D1 (n=4,8,16) | 0.81 units on scale | Standard Deviation 2.32 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C14D1 (n=8,17,14) | 0.29 units on scale | Standard Deviation 2.12 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Follow_Up (n=4,15,14) | 0.29 units on scale | Standard Deviation 1.72 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C8D1 (n=17,29,22) | 0.42 units on scale | Standard Deviation 1.74 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C15D1 (n=7,11,9) | 0.70 units on scale | Standard Deviation 2.36 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C42D1 (n=2,2,1) | 0.00 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: Baseline (n=41,43,40) | 2.18 units on scale | Standard Deviation 2.06 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C16D1 (n=7,17,14) | -0.01 units on scale | Standard Deviation 2.38 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C40D1 (n=2,2,2) | 0.43 units on scale | Standard Deviation 0.61 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C18D1 (n=6,14,9) | 0.61 units on scale | Standard Deviation 1.55 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C17D1 (n=5,11,6) | 1.17 units on scale | Standard Deviation 1.28 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C39D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C10D1 (n=14,27,21) | 0.77 units on scale | Standard Deviation 1.52 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C18D1 (n=6,14,9) | 1.00 units on scale | Standard Deviation 2.26 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C40D1 (n=2,2,2) | 0.25 units on scale | Standard Deviation 0.35 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C2D1 (n=37,37,37) | 0.80 units on scale | Standard Deviation 1.32 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C19D1 (n=4,8,6) | 1.04 units on scale | Standard Deviation 1.84 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C38D1 (n=2,2,1) | 0.86 units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C17D1 (n=5,11,6) | 0.72 units on scale | Standard Deviation 1.07 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Interference Scale: C20D1 (n=5,14,8) | 0.35 units on scale | Standard Deviation 2.07 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C37D1 (n=0,1,0) | NA units on scale | — |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2 | Severity Scale: C9D1 (n=11,24,21) | 0.76 units on scale | Standard Deviation 1.5 |
Secondary
Clearance (CL) For 5-Fluorouracil: Phase 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. CL for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 147.43 L/hr |
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 137.34 L/hr |
| Phase 2: Bevacizumab + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 128.28 L/hr |
| Phase 2: Bevacizumab + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 144.62 L/hr |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 99.36 L/hr |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Clearance (CL) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 53.92 L/hr |
Secondary
Clearance (CL) For Bevacizumab: Phase 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. CL for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Bevacizumab: Phase 1 | Cycle 1 Day 1 | 0.01 L/hr |
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Bevacizumab: Phase 1 | Cycle 2 Day 1 | 0.02 L/hr |
Secondary
Clearance (CL) For Irinotecan: Phase 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Irinotecan: Phase 1 | Cycle 1 Day 8 | 26.09 L/hr |
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Irinotecan: Phase 1 | Cycle 2 Day 1 | 27.34 L/hr |
Secondary
Clearance (CL) For Oxaliplatin: Phase 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. CL for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 27.51 L/hr |
| Phase 2: Axitinib + FOLFOX | Clearance (CL) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 24.29 L/hr |
| Phase 2: Bevacizumab + FOLFOX | Clearance (CL) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 30.74 L/hr |
| Phase 2: Bevacizumab + FOLFOX | Clearance (CL) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 24.56 L/hr |
Secondary
Duration of Response (DR): Phase 2
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR: disappearance of all lesions and no appearance of new lesions. PR: \>=30% decrease in sum of LD of target lesions taking as reference the baseline sum LD, without progression of nontarget lesions and no appearance of new lesions. Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.
Time frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
Population: ITT population included all randomized participants, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized. 'N' (Number of participants analyzed)= those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Axitinib + FOLFOX | Duration of Response (DR): Phase 2 | 434.0 days |
| Phase 2: Bevacizumab + FOLFOX | Duration of Response (DR): Phase 2 | NA days |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Duration of Response (DR): Phase 2 | 343.0 days |
Secondary
Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1
PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. Cmax for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 16160.85 ng/mL |
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 16249.77 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 34436.94 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 39730.46 ng/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 19622.74 ng/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 34180.87 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1
PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3.Cmax for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 1 Day 8 | 35.57 ng/mL |
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 2 Day 1 | 27.51 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 1 Day 8 | 27.14 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 2 Day 1 | 42.48 ng/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 1 Day 8 | 24.23 ng/mL |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1 | Cycle 2 Day 1 | 32.62 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1
PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. Cmax for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1 | Cycle 1 Day 1 | 26460.05 ng/mL |
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1 | Cycle 2 Day 1 | 26850.12 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1
Cmax for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1 | Cycle 1 Day 1 | 1910.25 ng/mL |
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1 | Cycle 2 Day 1 | 1788.69 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1
PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. Cmax for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 278.81 ng/mL |
| Phase 2: Axitinib + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 318.99 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 265.05 ng/mL |
| Phase 2: Bevacizumab + FOLFOX | Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 374.03 ng/mL |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK assessments were done only for cohort 1 to 5, as per planned analysis. Results for Cmin are not reported because Cmin could not be assessed from the data obtained from the study.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1
Time frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK assessments were done only for cohort 1 to 5, as per planned analysis. Results for Cmin are not reported because Cmin could not be assessed from the data obtained from the study.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK assessments were done only for cohort 1 to 5, as per planned analysis. Results for Cmin are not reported because Cmin could not be assessed from the data obtained from the study.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK assessments were done only for cohort 1 to 5, as per planned analysis. Results for Cmin are not reported because Cmin could not be assessed from the data obtained from the study.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK assessments were done only for cohort 1 to 5, as per planned analysis. Results for Cmin are not reported because Cmin could not be assessed from the data obtained from the study.
Secondary
Overall Survival (OS): Phase 2
Time in days from randomization date to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time frame: Every 3 months after discontinuation of study treatment until death due to any cause or 1 year after randomization of the last participant
Population: ITT population included all randomized participants , with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Axitinib + FOLFOX | Overall Survival (OS): Phase 2 | 552.0 days |
| Phase 2: Bevacizumab + FOLFOX | Overall Survival (OS): Phase 2 | 659.0 days |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Overall Survival (OS): Phase 2 | 601.0 days |
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.690495% CI: [0.656, 2.033]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.736495% CI: [0.676, 2.141]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.41495% CI: [0.535, 1.653]Log Rank
Secondary
Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. t1/2 for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 0.26 hours | Standard Deviation 0.218 |
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 0.25 hours | Standard Deviation 0.142 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 0.19 hours | Standard Deviation 0.069 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 0.14 hours | Standard Deviation 0.029 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 1 Day 1 | 0.39 hours | Standard Deviation 0.291 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1 | Cycle 2 Day 1 | 0.24 hours | Standard Deviation 0.131 |
Secondary
Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. t1/2 for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 1 Day 8 | 3.26 hours | Standard Deviation 3.943 |
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 2 Day 1 | 6.12 hours | Standard Deviation 7.45 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 1 Day 8 | 2.23 hours | Standard Deviation 0.702 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 2 Day 1 | 3.09 hours | Standard Deviation 0.889 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 1 Day 8 | 3.47 hours | Standard Deviation 2.82 |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1 | Cycle 2 Day 1 | 1.73 hours | Standard Deviation 0.456 |
Secondary
Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. t1/2 for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1 | Cycle 1 Day 1 | 205.97 hours | Standard Deviation 46.454 |
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1 | Cycle 2 Day 1 | 210.22 hours | Standard Deviation 55.317 |
Secondary
Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. t1/2 for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1 | Cycle 1 Day 1 | 6.45 hours | Standard Deviation 1.406 |
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1 | Cycle 2 Day 1 | 6.75 hours | Standard Deviation 0.886 |
Secondary
Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. t1/2 for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.
Time frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
Population: PK parameter analysis set included all treated participants who had at least 1 estimated PK parameters of primary interest. PK assessments were done only for cohort 1 to 5, as per planned analysis. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 20.63 hours | Standard Deviation 6.513 |
| Phase 2: Axitinib + FOLFOX | Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 23.30 hours | Standard Deviation 14.975 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1 | Cycle 1 Day 1 | 18.38 hours | Standard Deviation 3.004 |
| Phase 2: Bevacizumab + FOLFOX | Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1 | Cycle 2 Day 1 | 19.86 hours | Standard Deviation 4.11 |
Secondary
Progression-Free Survival (PFS): Phase 2
Time in days from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death). Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.
Time frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
Population: ITT population included all randomized participants, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Axitinib + FOLFOX | Progression-Free Survival (PFS): Phase 2 | 336 days |
| Phase 2: Bevacizumab + FOLFOX | Progression-Free Survival (PFS): Phase 2 | 485 days |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Progression-Free Survival (PFS): Phase 2 | 381 days |
Comparison: Hazard ratio and corresponding 95% confidence interval (CI) was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.569995% CI: [0.47, 2.45]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.216795% CI: [0.33, 1.61]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.874695% CI: [0.75, 2.98]Log Rank
Secondary
Time to Treatment Failure (TTF): Phase 2
TTF is defined as the time from the randomization to the date of the first documentation of PD, symptomatic deterioration, death due to any cause, or treatment discontinuation due to adverse event, refusal or other reasons. Progression: \>=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.
Time frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
Population: ITT population included all randomized participants, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Axitinib + FOLFOX | Time to Treatment Failure (TTF): Phase 2 | 187.0 days |
| Phase 2: Bevacizumab + FOLFOX | Time to Treatment Failure (TTF): Phase 2 | 241.0 days |
| Phase 2: Axitinib + Bevacizumab + FOLFOX | Time to Treatment Failure (TTF): Phase 2 | 238.0 days |
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.888495% CI: [0.81, 2.41]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.664895% CI: [0.66, 1.89]Log Rank
Comparison: Hazard ratio and corresponding 95% CI was calculated based on the Cox proportional hazards model stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no). One-sided p-value was derived from the log-rank test stratified by prior adjuvant chemotherapy (yes vs. no) and prior pelvic irradiation (yes vs. no).p-value: 0.806595% CI: [0.75, 2.07]Log Rank