Metastatic Colorectal Carcinoma
Conditions
Brief summary
This is a multicenter, open label Phase 1b/2 study in patients with metastatic colorectal carcinoma. The Phase 1b will identify the dose of the combination of PF-05212384 plus FOLFIRI. The randomized, two-arm Phase 2 portion will compare the efficacy and safety of PF-05212384 plus FOLFIRI to that of bevacizumab plus FOLFIRI. The study population will consist of patients with mCRC previously treated with an oxaliplatin-based regimen in the first line setting or who have progressed within 6 months of the end of an adjuvant oxaliplatin-based regimen.
Interventions
BIOLOGICALBevacizumab
5 mg/m\^2 every 2 weeks or 7.5 mg/m\^2 every 3 weeks
DRUGFOLFIRI
Full dose FOLFIRI regimen every 2 weeks
DRUGPF-05212384
PF-05212384 at the Recommended phase 2 dose (RP2D/MTD) weekly
DRUGFOLFIRI regimen
The RP2D/MTD dose of FOLFIRI regimen every 2 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced colorectal carcinoma. * Progression on prior oxaliplatin-containing regimen used in 1st line setting for mCRC or progression within 6 months of end of oxaliplatin-containing regimen in the adjuvant setting. * Tumor tissue available at time of screening for molecular profiling. * Adequate performance status. * Adequate glucose control, bone marrow, kidney, liver, and heart function.
Exclusion criteria
* Participation in other studies involving investigational drug(s) (Phases 1-4) before the current study begins and/or during study participation. * Prior irinotecan treatment. * Prior radiation to the pelvis or abdomen in the metastatic or locally advanced setting. * History of Gilbert's syndrome. * Active brain metastases. * Deep vein thrombosis in the preceding 2 months. * History of interstitial lung disease. * RAS (KRAS/NRAS) wild type mCRC not previously treated with an anti-EGFR containing regimen (unless contraindicated or not considered standard practice per clinical site or country guidelines).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | Day 1 up to Day 28 | DLTs were classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and defined as any of the following events judged to be attributed to the combination of PF-05212384 plus FOLFIRI: hematologic (febrile neutropenia or a sustained temperature \>=38 degrees Celcius for \>1 hour, grade \>=3 neutropenic infection, grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia); non-hematologic (grade \>=2 pneumonitis, grade \>=3 toxicities, toxicities which resulted in failure to deliver at least 75% of the planned total dose of PF-05212384 and/or 50% of the planned total dose of FOLFIRI during the first cycle, toxicities which resulted in delay of start of Cycle 2 by \>2 weeks of scheduled day (Day 43 of study), Grade 3 QTc prolongation). |
| Progression-Free Survival (PFS) | Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months) | Progression-free survival was the time from randomization the date to date of first documentation of progression or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All Causality AEs by System Organ Class (SOC) | Baseline up to final study evaluation (within 28 days of last dose) | An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. |
| Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Baseline up to final study evaluation (within 28 days of last dose) | An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AE grades were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. |
| Number of Participants With Hematological Test Abnormalities | Day 1 and Day 15 of each cycle | Number of participants with NCI CTCAE version 4.0 grade 1 to 4 hematological test abnormalities. |
| Number of Participants With Coagulation Test Abnormalities | Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles | Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Coagulation test abnormalities. |
| Number of Participants With Chemistry Test Abnormalities | Day 1 and Day 15 of each cycle | Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Chemistry test abnormalities. |
| Number of Participants With Urinalysis Test Abnormalities | Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles | Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Urinalysis test abnormalities. |
| Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1. | Maximum Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil |
| Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1. | Time to Reach Maximum Observed Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. | Area Under the Curve From Time Zero to Last Quantifiable Concentration of PF-05212384, and Irinotecan |
| Number of Participants With Best Overall Response (Phase 1B) | Every 8 weeks from Cycle 1 Day 1 until 28 days of last dose | Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented). |
| Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. | Terminal Elimination Half-Life of PF-05212384 and Irinotecan |
| Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | Baseline, Cycle 1 Day 1, and Cycle 2 Day 2 | Criteria for corrected QT interval using Fridericia's formula (QTcF) meeting potential clinical concern included: an absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>500 msec; an absolute change 30 - \<60, \>=60 msec. |
| Number of Participants With Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue | Baseline and Cycle 2 Day 17 | Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity. |
| Number of Participants With Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue | Baseline and Cycle 2 Day 17 | Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity. |
| Number of Participants With Best Overall Response (Phase 2) | Day 1 up to Day 28 | Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented). |
| Duration of Response (Phase 2) | Day 1 to Day 28 | Duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death. |
| Overall Survival (Phase 2) | Day 1 up to Day 28 | Overall survival is the time from randomization date to date of death due to any cause. |
| Number of Participants With Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2) | Baseline and Cycle 2 Day 17 | Biomarker evaluation were to be performed on these fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2) | Day 1 of each cycle | The FACT-C was to assess health-related quality of life and colorectal cancer (CRC)-related symptoms. It includes a total of 36 items, which are summarized into 6 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), CRC subscale (9 items) which addresses a subset of CRC concerns such as diarrhea. |
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time of PF-05212384 and Irinotecan |
| Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Baseline up to final study evaluation (within 28 days of last dose) | An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was considered treatment emergent if the event occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment; or the event was seen prior to the start of treatment but increased in CTCAE version 4.0 grade after the start of study treatment and within 28 days after final dose of study treatment. |
Countries
Canada, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m\^2, leucovorin 320 mg/m\^2, 5- fluorouracil (FU) 1920 mg/m\^2, and IV bolus of 5-FU 320 mg/m\^2 on Days 1 and 15 of each cycle. | 3 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2, 5- fluorouracil (FU) 2400 mg/m\^2, and IV bolus of 5-FU 400 mg/m\^2 on Days 1 and 15 of each cycle. | 4 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2, 5- fluorouracil (FU) 2400 mg/m\^2, and IV bolus of 5-FU 400 mg/m\^2 on Days 1 and 15 of each cycle. | 3 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 Participants received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2, 5- fluorouracil (FU) 2400 mg/m\^2, and IV bolus of 5-FU 400 mg/m\^2 on Days 1 and 15 of each cycle. | 5 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 Participants received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2, 5- fluorouracil (FU) 2400 mg/m\^2, and IV bolus of 5-FU 400 mg/m\^2 on Days 1 and 15 of each cycle. | 3 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 11.7 | 54.3 years STANDARD_DEVIATION 10.1 | 63.3 years STANDARD_DEVIATION 11.6 | 65.8 years STANDARD_DEVIATION 9 | 54.3 years STANDARD_DEVIATION 5.5 | 56.9 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 11 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 | 2 / 3 | 2 / 5 | 3 / 3 |
Outcome results
Primary
Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy
DLTs were classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and defined as any of the following events judged to be attributed to the combination of PF-05212384 plus FOLFIRI: hematologic (febrile neutropenia or a sustained temperature \>=38 degrees Celcius for \>1 hour, grade \>=3 neutropenic infection, grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia); non-hematologic (grade \>=2 pneumonitis, grade \>=3 toxicities, toxicities which resulted in failure to deliver at least 75% of the planned total dose of PF-05212384 and/or 50% of the planned total dose of FOLFIRI during the first cycle, toxicities which resulted in delay of start of Cycle 2 by \>2 weeks of scheduled day (Day 43 of study), Grade 3 QTc prolongation).
Time frame: Day 1 up to Day 28
Population: The dose limiting toxicity analysis set included participants in Phase 1B who started treatment and who did not have a major treatment deviation in the lead-in period and the first cycle of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | 0 percentage of participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | 0 percentage of participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | 0 percentage of participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | 20.0 percentage of participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy | 66.7 percentage of participants |
Primary
Progression-Free Survival (PFS)
Progression-free survival was the time from randomization the date to date of first documentation of progression or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)
Population: PFS was the primary efficacy endpoint for the study and was only to be assessed in the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2.
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan
Area Under the Curve From Time Zero to Last Quantifiable Concentration of PF-05212384, and Irinotecan
Time frame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384 (n=3,4,1,5,3) | 11460 ng*hr/mL | Geometric Coefficient of Variation 22 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | Irinotecan (n=3,4,1,4,3) | 12510 ng*hr/mL | Geometric Coefficient of Variation 8 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384 (n=3,4,1,5,3) | 9129 ng*hr/mL | Geometric Coefficient of Variation 33 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | Irinotecan (n=3,4,1,4,3) | 9164 ng*hr/mL | Geometric Coefficient of Variation 53 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384 (n=3,4,1,5,3) | 30700 ng*hr/mL | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | Irinotecan (n=3,4,1,4,3) | 8050 ng*hr/mL | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | Irinotecan (n=3,4,1,4,3) | 10340 ng*hr/mL | Geometric Coefficient of Variation 15 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384 (n=3,4,1,5,3) | 13570 ng*hr/mL | Geometric Coefficient of Variation 40 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | PF-05212384 (n=3,4,1,5,3) | 14760 ng*hr/mL | Geometric Coefficient of Variation 34 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan | Irinotecan (n=3,4,1,4,3) | 11030 ng*hr/mL | Geometric Coefficient of Variation 28 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time of PF-05212384 and Irinotecan
Time frame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384 | 11820 ng*hr/mL | Geometric Coefficient of Variation 22 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | Irinotecan | 13120 ng*hr/mL | Geometric Coefficient of Variation 10 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384 | 9289 ng*hr/mL | Geometric Coefficient of Variation 32 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | Irinotecan | 9709 ng*hr/mL | Geometric Coefficient of Variation 54 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384 | 30900 ng*hr/mL | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | Irinotecan | 8350 ng*hr/mL | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | Irinotecan | 10900 ng*hr/mL | Geometric Coefficient of Variation 16 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384 | 13830 ng*hr/mL | Geometric Coefficient of Variation 40 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | PF-05212384 | 15270 ng*hr/mL | Geometric Coefficient of Variation 34 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan | Irinotecan | 11560 ng*hr/mL | Geometric Coefficient of Variation 29 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2)
The FACT-C was to assess health-related quality of life and colorectal cancer (CRC)-related symptoms. It includes a total of 36 items, which are summarized into 6 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), CRC subscale (9 items) which addresses a subset of CRC concerns such as diarrhea.
Time frame: Day 1 of each cycle
Population: FACT-C was only applicable to the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, no data were collected for Phase 2.
Secondary
Duration of Response (Phase 2)
Duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death.
Time frame: Day 1 to Day 28
Population: As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.
Secondary
Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
Maximum Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
Time frame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 8245 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 25 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 18390 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 85 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1782 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 4 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1323 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 43 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 6554 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 66 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 18950 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 41 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1550 nanogram (ng)/milliliter (mL) | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 33470 nanogram (ng)/milliliter (mL) | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 44000 nanogram (ng)/milliliter (mL) | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 8222 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 35 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 26790 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 18 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1585 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 17 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1755 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 6 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 10250 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 11 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 26920 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 3 |
Secondary
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
Criteria for corrected QT interval using Fridericia's formula (QTcF) meeting potential clinical concern included: an absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>500 msec; an absolute change 30 - \<60, \>=60 msec.
Time frame: Baseline, Cycle 1 Day 1, and Cycle 2 Day 2
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval <450 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >60 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >30 to =<60 msec | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >480-500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval 450-480 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase =< 30 msec | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase =< 30 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval 450-480 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval <450 msec | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >30 to =<60 msec | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >480-500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >60 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval <450 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval 450-480 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >480-500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase =< 30 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >30 to =<60 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >60 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >480-500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase =< 30 msec | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval 450-480 msec | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >60 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >30 to =<60 msec | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval <450 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >480-500 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >60 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase >30 to =<60 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval increase =< 30 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval 450-480 msec | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval <450 msec | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants Meeting Maximum Post-Baseline QTc Interval Values | QTcF Interval >500 msec | 0 participants |
Secondary
Number of Participants With All Causality AEs by System Organ Class (SOC)
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug.
Time frame: Baseline up to final study evaluation (within 28 days of last dose)
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Blood and lymphatic system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Injury, poisoning and procedural complications | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Musculoskeletal and connective tissue disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Investigations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Skin and subcutaneous tissue disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Metabolism and nutrition disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Gastrointestinal disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Respiratory, thoracic and mediastinal disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | General disorders & administration site conditions | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Vascular disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Renal and urinary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Hepatobiliary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Eye disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Psychiatric disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Immune system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Nervous system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Infections and infestations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Immune system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Renal and urinary disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Injury, poisoning and procedural complications | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Skin and subcutaneous tissue disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Eye disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Metabolism and nutrition disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Nervous system disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Investigations | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Hepatobiliary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Blood and lymphatic system disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Psychiatric disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Gastrointestinal disorders | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Vascular disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Respiratory, thoracic and mediastinal disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Musculoskeletal and connective tissue disorders | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | Infections and infestations | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality AEs by System Organ Class (SOC) | General disorders & administration site conditions | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Musculoskeletal and connective tissue disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Blood and lymphatic system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Eye disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Gastrointestinal disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | General disorders & administration site conditions | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Hepatobiliary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Immune system disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Infections and infestations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Injury, poisoning and procedural complications | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Investigations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Metabolism and nutrition disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Nervous system disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Psychiatric disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Renal and urinary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Respiratory, thoracic and mediastinal disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Skin and subcutaneous tissue disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality AEs by System Organ Class (SOC) | Vascular disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Injury, poisoning and procedural complications | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Infections and infestations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Musculoskeletal and connective tissue disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Immune system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Nervous system disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Hepatobiliary disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Psychiatric disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | General disorders & administration site conditions | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Blood and lymphatic system disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Renal and urinary disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Gastrointestinal disorders | 5 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Respiratory, thoracic and mediastinal disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Eye disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Vascular disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Investigations | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Skin and subcutaneous tissue disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Metabolism and nutrition disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Metabolism and nutrition disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Renal and urinary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Gastrointestinal disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Musculoskeletal and connective tissue disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Immune system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Investigations | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Skin and subcutaneous tissue disorders | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Vascular disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Nervous system disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Hepatobiliary disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Infections and infestations | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Blood and lymphatic system disorders | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Respiratory, thoracic and mediastinal disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Psychiatric disorders | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | General disorders & administration site conditions | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Eye disorders | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality AEs by System Organ Class (SOC) | Injury, poisoning and procedural complications | 0 participants |
Secondary
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was considered treatment emergent if the event occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment; or the event was seen prior to the start of treatment but increased in CTCAE version 4.0 grade after the start of study treatment and within 28 days after final dose of study treatment.
Time frame: Baseline up to final study evaluation (within 28 days of last dose)
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number of Participants D/C'd FOLFIRI Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd PF-05212384 Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 3 or 4 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with SAEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd Study Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 5 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number (#) of Participants with AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 5 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd Study Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd PF-05212384 Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number of Participants D/C'd FOLFIRI Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number (#) of Participants with AEs | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with SAEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 3 or 4 AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd Study Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 5 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd PF-05212384 Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number (#) of Participants with AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number of Participants D/C'd FOLFIRI Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 3 or 4 AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with SAEs | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number of Participants D/C'd FOLFIRI Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 5 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 3 or 4 AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number (#) of Participants with AEs | 5 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with SAEs | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd PF-05212384 Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd Study Due to AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd PF-05212384 Due to AEs | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number of Participants D/C'd FOLFIRI Due to AEs | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | Number (#) of Participants with AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 5 AEs | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with Grade 3 or 4 AEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants with SAEs | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness | # of Participants D/C'd Study Due to AEs | 0 participants |
Secondary
Number of Participants With Best Overall Response (Phase 1B)
Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).
Time frame: Every 8 weeks from Cycle 1 Day 1 until 28 days of last dose
Population: All participants in the full analysis (FA) set who had measureable disease and an adequate baseline assessment of the disease.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Best Overall Response (Phase 1B) | PD | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Best Overall Response (Phase 1B) | SD | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Best Overall Response (Phase 1B) | PR | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Best Overall Response (Phase 1B) | Indeterminant | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Best Overall Response (Phase 1B) | PD | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Best Overall Response (Phase 1B) | Indeterminant | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Best Overall Response (Phase 1B) | SD | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Best Overall Response (Phase 1B) | PR | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Best Overall Response (Phase 1B) | Indeterminant | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Best Overall Response (Phase 1B) | SD | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Best Overall Response (Phase 1B) | PR | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Best Overall Response (Phase 1B) | PD | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Best Overall Response (Phase 1B) | PD | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Best Overall Response (Phase 1B) | SD | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Best Overall Response (Phase 1B) | Indeterminant | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Best Overall Response (Phase 1B) | PR | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Best Overall Response (Phase 1B) | Indeterminant | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Best Overall Response (Phase 1B) | PR | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Best Overall Response (Phase 1B) | SD | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Best Overall Response (Phase 1B) | PD | 1 participants |
Secondary
Number of Participants With Best Overall Response (Phase 2)
Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).
Time frame: Day 1 up to Day 28
Population: As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.
Secondary
Number of Participants With Chemistry Test Abnormalities
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Chemistry test abnormalities.
Time frame: Day 1 and Day 15 of each cycle
Population: All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hyperkalemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Bilirubin (total) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypokalemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Alkaline phosphatase | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Alanine aminotransferase | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hyperglycemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Creatinine | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypocalcemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hyponatremia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Aspartate aminotransferase | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypoglycemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypomagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypoalbuminemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypermagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Chemistry Test Abnormalities | Hypohphosphatemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Alkaline phosphatase | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypoglycemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hyperkalemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypokalemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypomagnesemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Aspartate aminotransferase | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Bilirubin (total) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Creatinine | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypohphosphatemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hyperglycemia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypermagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypoalbuminemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hyponatremia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Hypocalcemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Chemistry Test Abnormalities | Alanine aminotransferase | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Alanine aminotransferase | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Aspartate aminotransferase | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypocalcemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypermagnesemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypokalemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hyponatremia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypomagnesemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypoglycemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Creatinine | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hyperkalemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypoalbuminemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hypohphosphatemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Alkaline phosphatase | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Hyperglycemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Chemistry Test Abnormalities | Bilirubin (total) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hyperkalemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Alanine aminotransferase | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Alkaline phosphatase | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Aspartate aminotransferase | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Bilirubin (total) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Creatinine | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hyperglycemia | 5 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypermagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypoalbuminemia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypocalcemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypoglycemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypokalemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypomagnesemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hyponatremia | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Chemistry Test Abnormalities | Hypohphosphatemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypomagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypocalcemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypoalbuminemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypermagnesemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Alanine aminotransferase | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hyponatremia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hyperglycemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Creatinine | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Bilirubin (total) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hyperkalemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypohphosphatemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Aspartate aminotransferase | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypokalemia | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Hypoglycemia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Chemistry Test Abnormalities | Alkaline phosphatase | 1 participants |
Secondary
Number of Participants With Coagulation Test Abnormalities
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Coagulation test abnormalities.
Time frame: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
Population: All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Coagulation Test Abnormalities | Partial thromboplastin time (N=3, 4, 3, 5, 2) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Coagulation Test Abnormalities | PT INR (N=3, 4, 3, 5, 2) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Coagulation Test Abnormalities | Prothrombin time (PT) (N=3, 3,2, 5, 1) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Coagulation Test Abnormalities | Prothrombin time (PT) (N=3, 3,2, 5, 1) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Coagulation Test Abnormalities | Partial thromboplastin time (N=3, 4, 3, 5, 2) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Coagulation Test Abnormalities | PT INR (N=3, 4, 3, 5, 2) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Coagulation Test Abnormalities | Prothrombin time (PT) (N=3, 3,2, 5, 1) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Coagulation Test Abnormalities | Partial thromboplastin time (N=3, 4, 3, 5, 2) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Coagulation Test Abnormalities | PT INR (N=3, 4, 3, 5, 2) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Coagulation Test Abnormalities | Partial thromboplastin time (N=3, 4, 3, 5, 2) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Coagulation Test Abnormalities | PT INR (N=3, 4, 3, 5, 2) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Coagulation Test Abnormalities | Prothrombin time (PT) (N=3, 3,2, 5, 1) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Coagulation Test Abnormalities | Prothrombin time (PT) (N=3, 3,2, 5, 1) | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Coagulation Test Abnormalities | Partial thromboplastin time (N=3, 4, 3, 5, 2) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Coagulation Test Abnormalities | PT INR (N=3, 4, 3, 5, 2) | 1 participants |
Secondary
Number of Participants With Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2)
Biomarker evaluation were to be performed on these fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
Time frame: Baseline and Cycle 2 Day 17
Population: Levels of signaling proteins in biopsied tumor tissue was the secondary endpoint for the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, no data were collected for Phase 2.
Secondary
Number of Participants With Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue
Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
Time frame: Baseline and Cycle 2 Day 17
Population: Paired fresh tumor biopsies were only done in 1 subject but not summarized.
Secondary
Number of Participants With Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue
Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
Time frame: Baseline and Cycle 2 Day 17
Population: Paired fresh tumor biopsies were only done in 1 subject but not summarized.
Secondary
Number of Participants With Hematological Test Abnormalities
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 hematological test abnormalities.
Time frame: Day 1 and Day 15 of each cycle
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Neutrophils (Absolute) | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Hemoglobin increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Platelets | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | White blood cells | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Lymphocyte count increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Lymphopenia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Hematological Test Abnormalities | Anemia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Hemoglobin increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Lymphopenia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Anemia | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Lymphocyte count increased | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | White blood cells | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Neutrophils (Absolute) | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Hematological Test Abnormalities | Platelets | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | White blood cells | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Hemoglobin increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Platelets | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Neutrophils (Absolute) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Lymphopenia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Anemia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Hematological Test Abnormalities | Lymphocyte count increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Lymphocyte count increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | White blood cells | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Hemoglobin increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Platelets | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Lymphopenia | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Anemia | 5 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Hematological Test Abnormalities | Neutrophils (Absolute) | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | White blood cells | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Anemia | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Hemoglobin increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Lymphocyte count increased | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Lymphopenia | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Platelets | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Hematological Test Abnormalities | Neutrophils (Absolute) | 2 participants |
Secondary
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AE grades were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.
Time frame: Baseline up to final study evaluation (within 28 days of last dose)
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 1 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 2 | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 3 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 4 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 5 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, total | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 5 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, total | 4 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 1 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 3 | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 4 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 2 | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 4 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 5 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 1 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 3 | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 2 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, total | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 4 | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 2 | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 3 | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, total | 5 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 5 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 1 | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 5 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 3 | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 2 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, total | 3 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 4 | 0 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade | Any AEs, Grade 1 | 0 participants |
Secondary
Number of Participants With Urinalysis Test Abnormalities
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Urinalysis test abnormalities.
Time frame: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Number of Participants With Urinalysis Test Abnormalities | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Number of Participants With Urinalysis Test Abnormalities | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Number of Participants With Urinalysis Test Abnormalities | 1 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Number of Participants With Urinalysis Test Abnormalities | 2 participants |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Number of Participants With Urinalysis Test Abnormalities | 2 participants |
Secondary
Overall Survival (Phase 2)
Overall survival is the time from randomization date to date of death due to any cause.
Time frame: Day 1 up to Day 28
Population: As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.
Secondary
Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan
Terminal Elimination Half-Life of PF-05212384 and Irinotecan
Time frame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384 | 33.63 hour | Standard Deviation 1.3503 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | Irinotecan | 5.127 hour | Standard Deviation 0.70692 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384 | 27.90 hour | Standard Deviation 3.3695 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | Irinotecan | 5.533 hour | Standard Deviation 1.1621 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384 | 29.2 hour | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | Irinotecan | 4.97 hour | — |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | Irinotecan | 5.360 hour | Standard Deviation 0.40817 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384 | 29.18 hour | Standard Deviation 6.9909 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | PF-05212384 | 36.97 hour | Standard Deviation 1.9035 |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan | Irinotecan | 5.107 hour | Standard Deviation 0.40427 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
Time to Reach Maximum Observed Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
Time frame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 0.500 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 0.0830 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 2.02 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 2.04 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 0.550 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 0.167 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 1.95 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 0.500 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 0.0830 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 0.500 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 0.125 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 2.25 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Irinotecan (n=3,4,1,5,3) | 2.00 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | PF-05212384 (n=3,4,2,5,3) | 0.500 hour (hr) |
| PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 | Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil | Fluorouracil (n=3,4,1,4,3) | 0.150 hour (hr) |