Advanced Gastrointestinal Cancer
Conditions
Brief summary
This is an open label, multi-center, Phase 1/2 dose escalation study of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan.
Detailed description
This is an open label, multi-center, Phase 1/2 dose escalation study of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan. A study cycle will consist of daily and continuous oral administration of BBI608 for four weeks (28 days) in combination with FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan.
Interventions
DRUGBBI608
DRUGFluorouracil
DRUGOxaliplatin
DRUGLeucovorin
DRUGIrinotecan
DRUGBevacizumab
DRUGCapecitabine
DRUGRegorafenib
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NON_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
1. Signed written informed consent 2. A histologically confirmed solid tumor of the gastrointestinal tract including 1. Advanced unresectable, metastatic or recurrent colorectal carcinoma (CRC) for which treatment with FOLFOX6 with or without bevacizumab, FOLFIRI with or without bevacizumab, CAPOX, or regorafenib would be acceptable as determined by the Investigator. FOLFIRI/XELIRI-refractory patients with CRC enrolling on the FOLFIRI study arm must have failed treatment with one FOLFIRI pr XELIRI with or without bevacizumab regimen for unresectable or metastatic disease. Treatment failure is defined as progression of disease (clinical or radiologic) during treatment with FOLFIRI with or without bevacizumab or \< 3 months after the last dose of treatment with FOLFIRI with or without bevacizumab. Patients with CRC enrolling on the regorafenib arm of this study will have previously received at least two previous lines of therapy for advanced colorectal cancer, and will have previously received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Patients with K-ras wild type tumors enrolling on the regorafenib arm will also have previously received either cetuximab or panitumumab. 2. Hepatocellular carcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator. 3. Pancreatic adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator. 4. Cholangiocarcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator. 5. Gastric, GEJ or esophageal adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator. 3. Patients may be treatment naïve, or may have received standard chemotherapy; including regimens containing a fluoropyrimidine, or oxaliplatin, or irinotecan, or regorafenib, or bevacizumab. 4. ≥18 years of age. 5. Karnofsky performance status score ≥70%. 6. Male or female patients of child-producing potential agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose. 7. Females of childbearing potential have a negative serum pregnancy test. 8. AST level ≤2.5 x ULN and ALT ≤ 2.5 × ULN. For patients with liver metastases, AST ≤3.5 x ULN, and AST ≤3.5 x ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor. 9. Hemoglobin ≥10 g/dl. 10. Total bilirubin level ≤1.5 × ULN. 11. Creatinine ≤1.5 x ULN or creatinine clearance \>60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal (as determined by Cockcroft-Gault equation). 12. Absolute neutrophil count ≥ 1.5 x 10\^9/L. 13. Platelets ≥100 x 10\^9/L. 14. Life expectancy estimated at ≥3 months.
Exclusion criteria
1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of the first dose of BBI608. 2. Major surgery within 4 weeks prior to first dose. 3. Any known untreated brain metastases. Treated subjects must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated. 4. Pregnant or breastfeeding. 5. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent 6. Unable or unwilling to swallow BBI608 capsules daily. 7. Prior treatment with BBI608. 8. Uncontrolled intercurrent illness 9. For patients to be treated with a regimen containing 5-fluorouracil/leucovorin: 1. Known hypersensitivity to 5-fluorouracil/leucovorin 2. Known dihydropyrimidine dehydrogenase (DPD) deficiency 10. For patients to be treated with a regimen containing capecitabine: 1. Known hypersensitivity to capecitabine 2. Known dihydropyrimidine dehydrogenase (DPD) deficiency 3. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent 11. For patients to be treated with a regimen containing oxaliplatin: 1. Neurosensory neuropathy ≥ grade 2 at baseline 2. Known hypersensitivity to oxaliplatin or other platinum containing compounds 12. For patients to be treated with a regimen containing irinotecan: 1. Known hypersensitivity to irinotecan 2. Abnormal glucuronidation of bilirubin 13. For patients to be treated with a regimen containing bevacizumab: 1. Current uncontrolled hypertension as well as prior history of hypertensive crisis or hypertensive encephalopathy 2. History of cardiac disease: congestive heart failure (CHF) \> NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy 3. History of arterial thrombotic or embolic events (within 6 months prior to study entry) 4. Significant vascular disease 5. Evidence of bleeding diathesis or clinically significant coagulopathy 6. Major surgical procedure within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure within 7 days prior to study enrollment 7. Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥ 2+. 8. History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months 9. Ongoing serious, non-healing wound, ulcer, or bone fracture 10. Known hypersensitivity to any component of bevacizumab 11. History of reversible posterior leukoencephalopathy syndrome (RPLS) 14. For patients to be treated with a regimen containing regorafenib: 1. History of cardiac disease: congestive heart failure (CHF) \> NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy 2. Current uncontrolled hypertension 3. Interstitial lung disease with ongoing signs and symptoms at the time of screening 4. History of HIV infection or chronic hepatitis B or C 5. Active clinically serious infections 6. History of arterial or embolic events (within 6 months prior to study entry) 7. Liver cirrhosis ≥ Child-Pugh class B with uncontrolled ascites 8. History of RPLS 9. Ongoing serious, non-healing wound, ulcer, or bone fracture 10. Evidence of bleeding diathesis or a clinically significant coagulopathy 11. Renal failure requiring hemo- or peritoneal dialysis 12. Persistent proteinuria of CTCAE grade 3 (\>3.5g/24 hours) 13. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent 14. Known hypersensitivity to regorafenib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events | The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months. | Assessment of safety of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan in participants with advanced gastrointestinal malignancies by reporting of adverse events and serious adverse events |
| The Objective Response Rate of Napabucasin Administered in Combination in FOLFIRI in Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months | Assessment of the objective response rate (ORR) of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response who have measurable disease at baseline imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months. | To determine the anti-tumor activity (specifically the disease control rate) of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1. |
| Disease Control Rate of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months | To determine the disease control rate of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1. |
| Determination of the Maximum Observed Concentration (Cmax) and Area Under the Plasma Concentration vs. Time Curve (AUClast) | Blood samples drawn on days 1, 2, 15, 16, 21, and 22 of the first study cycle | To determine the maximum concentration of napabucasin and the area under the plasma concentration vs. time curve of napabucasin when administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib. |
| Overall Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 36 months. | The effect of napabucasin given in combination with FOLFIRI on Overall Survival (OS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. |
| Progression Free Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to thirty six months | The effect of napabucasin given in combination with FOLFIRI on Progression Free Survival (PFS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. PFS of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. |
| Pharmacodynamics | Day 1 of cycle 2 | To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin |
Countries
Canada, United States
Participant flow
Recruitment details
495 participants were enrolled between March 2014 and September 2017.
Pre-assignment details
Participants who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Napabucasin Plus FOLFOX6 All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily, in combination with FOLFOX6 regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously starting on Day 1 of Cycle 1, after the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous intravenous (IV) infusion. | 115 |
| Napabucasin Plus FOLFOX6 Plus Bevacizumab All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily, in combination with FOLFOX6 plus bevacizumab regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously over 2 hours starting on Day1 of Cycle 1, following the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous IV infusion. Bevacizumab 5 mg/kg was administered intravenously following the oxaliplatin/leucovorin infusion. | 41 |
| Napabucasin Plus CAPOX All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily, in combination with CAPOX regimen. The CAPOX regimen was administered orally (capecitabine) and by IV (oxaliplatin). Starting on Day 1 of Cycle 1, capecitabine 850 mg/m2 was administered orally BID following the first daily dose of napabucasin for 14 consecutive days and repeated every 21 days. Oxaliplatin 130 mg/m2 was administered intravenously over 2 hours, following the first daily dose of napabucasin starting on Day 1 of Cycle 1 and repeated every 21 days thereafter. If capecitabine was tolerated at the 850 mg/m2 BID dose, the dosage could have been increased to 1000 mg/m2 BID as tolerated after the first cycle. | 87 |
| Napabucasin Plus FOLFIRI All participants who were enrolled to Arm D to receive napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter. | 156 |
| Napabucasin Plus FOLFIRI Plus Bevacizumab All participants who were enrolled to Arm E to receive napabucasin administered orally, twice daily, in combination with FOLFIRI plus bevacizumab regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5 FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. Bevacizumab 5 mg/kg was administered intravenously following the irinotecan/leucovorin infusion. This regimen was repeated every 14 days thereafter. | 40 |
| Napabucasin Plus Regorafenib All participants who were enrolled to Arm F to receive napabucasin administered orally, twice daily, in combination with regorafenib 120 mg, administered orally once daily with a low-fat meal, starting on Day 1 of Cycle 1 for 21 consecutive days of every 28 days thereafter. If regorafenib was tolerated in the first cycle, the dosage could have been increased to 160 mg once daily as tolerated after the first cycle. | 54 |
| Napabucasin Plus Irinotecan All participants who were enrolled to Arm G to receive napabucasin administered orally, twice daily, in combination with irinotecan 180 mg/m2, administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. This regimen was repeated every 14 days thereafter. | 2 |
| Total | 495 |
Baseline characteristics
| Characteristic | Napabucasin Plus FOLFOX6 | Total | Napabucasin Plus Irinotecan | Napabucasin Plus Regorafenib | Napabucasin Plus FOLFIRI Plus Bevacizumab | Napabucasin Plus FOLFIRI | Napabucasin Plus CAPOX | Napabucasin Plus FOLFOX6 Plus Bevacizumab |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.26 | 59.4 years STANDARD_DEVIATION 11.42 | 73.0 years STANDARD_DEVIATION 1.41 | 57.5 years STANDARD_DEVIATION 11.56 | 55.8 years STANDARD_DEVIATION 7.25 | 58.3 years STANDARD_DEVIATION 12.18 | 62.7 years STANDARD_DEVIATION 11.69 | 55.4 years STANDARD_DEVIATION 13.54 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 16 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 10 Participants | 43 Participants | 0 Participants | 4 Participants | 4 Participants | 14 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 99 Participants | 426 Participants | 1 Participants | 49 Participants | 35 Participants | 134 Participants | 73 Participants | 35 Participants |
| Sex: Female, Male Female | 49 Participants | 189 Participants | 1 Participants | 28 Participants | 15 Participants | 52 Participants | 32 Participants | 12 Participants |
| Sex: Female, Male Male | 66 Participants | 306 Participants | 1 Participants | 26 Participants | 25 Participants | 104 Participants | 55 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 104 / 115 | 31 / 41 | 82 / 87 | 129 / 156 | 33 / 40 | 50 / 54 | 2 / 2 |
| other Total, other adverse events | 115 / 115 | 41 / 41 | 87 / 87 | 156 / 156 | 40 / 40 | 54 / 54 | 2 / 2 |
| serious Total, serious adverse events | 52 / 115 | 10 / 41 | 40 / 87 | 58 / 156 | 16 / 40 | 23 / 54 | 2 / 2 |
Outcome results
Primary
Number of Participants With Adverse Events and Serious Adverse Events
Assessment of safety of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan in participants with advanced gastrointestinal malignancies by reporting of adverse events and serious adverse events
Time frame: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | Number of Participants With Adverse Events and Serious Adverse Events | 115 Participants |
| Napabucasin Plus FOLFOX6 Plus Bevacizumab | Number of Participants With Adverse Events and Serious Adverse Events | 41 Participants |
| Napabucasin Plus CAPOX | Number of Participants With Adverse Events and Serious Adverse Events | 87 Participants |
| Napabucasin Plus FOLFIRI | Number of Participants With Adverse Events and Serious Adverse Events | 156 Participants |
| Napabucasin Plus FOLFIRI Plus Bevacizumab | Number of Participants With Adverse Events and Serious Adverse Events | 40 Participants |
| Napabucasin Plus Regorafenib | Number of Participants With Adverse Events and Serious Adverse Events | 54 Participants |
| Napabucasin Plus Irinotecan | Number of Participants With Adverse Events and Serious Adverse Events | 2 Participants |
Primary
The Objective Response Rate of Napabucasin Administered in Combination in FOLFIRI in Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer
Assessment of the objective response rate (ORR) of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response who have measurable disease at baseline imaging.
Time frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Population: Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer. Patients in this subgroup also had a baseline scan and at least 1 disease assessment following the initiation of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | The Objective Response Rate of Napabucasin Administered in Combination in FOLFIRI in Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | 0 percentage of participants |
Secondary
Determination of the Maximum Observed Concentration (Cmax) and Area Under the Plasma Concentration vs. Time Curve (AUClast)
To determine the maximum concentration of napabucasin and the area under the plasma concentration vs. time curve of napabucasin when administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib.
Time frame: Blood samples drawn on days 1, 2, 15, 16, 21, and 22 of the first study cycle
Population: Sponsor's decision to terminate further development of the napabucasin program. Data collection and analysis were therefore not conducted as planned.
Secondary
Disease Control Rate
To determine the anti-tumor activity (specifically the disease control rate) of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1.
Time frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months.
Population: Patients who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | Disease Control Rate | 54.7 percentage of participants |
| Napabucasin Plus FOLFOX6 Plus Bevacizumab | Disease Control Rate | 76.2 percentage of participants |
| Napabucasin Plus CAPOX | Disease Control Rate | 55.3 percentage of participants |
| Napabucasin Plus FOLFIRI | Disease Control Rate | 65.7 percentage of participants |
| Napabucasin Plus FOLFIRI Plus Bevacizumab | Disease Control Rate | 87.0 percentage of participants |
| Napabucasin Plus Regorafenib | Disease Control Rate | 34.4 percentage of participants |
| Napabucasin Plus Irinotecan | Disease Control Rate | 100 percentage of participants |
Secondary
Disease Control Rate of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer
To determine the disease control rate of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1.
Time frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Population: Patients with FOLFIRI/XELIRI refractory metastatic colorectal cancer who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | Disease Control Rate of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | 56.9 percentage of participants |
Secondary
Overall Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer
The effect of napabucasin given in combination with FOLFIRI on Overall Survival (OS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer.
Time frame: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 36 months.
Population: Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | Overall Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | 8.97 months |
Secondary
Pharmacodynamics
To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin
Time frame: Day 1 of cycle 2
Population: No on-treatment biopsies were performed therefore no pharmacodynamic testing on tumor tissue was conducted.
Secondary
Progression Free Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer
The effect of napabucasin given in combination with FOLFIRI on Progression Free Survival (PFS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. PFS of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer.
Time frame: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to thirty six months
Population: Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer. Patients in this subgroup also had a baseline scan and at least 1 on study scan or died from any cause.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Napabucasin Plus FOLFOX6 | Progression Free Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer | 20.82 months |