A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer
A Phase Ib/II Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer
1 other identifier
interventional
495
2 countries
15
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2014
Longer than P75 for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 20, 2013
CompletedFirst Posted
Study publicly available on registry
December 31, 2013
CompletedStudy Start
First participant enrolled
January 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2019
CompletedResults Posted
Study results publicly available
September 20, 2021
CompletedNovember 15, 2023
November 1, 2023
5.2 years
December 20, 2013
July 23, 2021
November 13, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
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
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.
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.
From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Secondary Outcomes (6)
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
Pharmacodynamics
Day 1 of cycle 2
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.
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
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
- +1 more secondary outcomes
Study Arms (7)
ARM A- BBI608 in combination with FOLFOX6
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Oxaliplatin 85 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2 over 46-48 hours) continuous intravenous infusion. This regimen will be repeated every 14 days thereafter.
ARM B- BBI608 in combination with FOLFOX6 and Bevacizumab
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Oxaliplatin 85 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2 over 46-48 hours) continuous intravenous infusion. Bevacizumab 5 mg/kg will be administered intravenously following oxaliplatin/leucovorin infusion. This regimen will be repeated every 14 days thereafter.
ARM C- BBI608 in combination with CAPOX
EXPERIMENTALBBI608 is administered orally twice daily, continuously. CAPOX regimen will be administered orally (capecitabine) and IV (oxaliplatin). Capecitabine 850 mg/m\^2 will be administered orally twice-daily for 14 consecutive days and be repeated every 21 days. Oxaliplatin will be administered IV and be repeated every 21 days thereafter. If capecitabine is tolerated at the 850 mg/m\^2 twice daily dose, dosage may be increased to 1000 mg/m\^2 twice daily as tolerated after the first cycle.
ARM D- BBI608 in combination with FOLFIRI
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated every 14 days thereafter.
ARM E- BBI608 in combination with FOLFIRI and Bevacizumab
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. Bevacizumab 5 mg/kg will be administered intravenously following oxaliplatin/leucovorin infusion. This regimen will be repeated every 14 days thereafter.
ARM F- BBI608 in combination with Regorafenib
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Regorafenib 120 mg will be administered orally once daily, with a low-fat meal and be continued for 21 consecutive days of every 28 days thereafter. If regorafenib is tolerated in the first cycle, dosage may be increased to 160 mg once daily as tolerated after the first cycle.
Arm G- BBI608 in combination with Irinotecan
EXPERIMENTALBBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 will be administered intravenously. This regimen will be repeated every 14 days thereafter.
Interventions
Eligibility Criteria
You may qualify if:
- Signed written informed consent
- A histologically confirmed solid tumor of the gastrointestinal tract including
- 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.
- Hepatocellular carcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator.
- Pancreatic adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
- Cholangiocarcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator.
- Gastric, GEJ or esophageal adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
- Patients may be treatment naïve, or may have received standard chemotherapy; including regimens containing a fluoropyrimidine, or oxaliplatin, or irinotecan, or regorafenib, or bevacizumab.
- ≥18 years of age.
- Karnofsky performance status score ≥70%.
- 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.
- Females of childbearing potential have a negative serum pregnancy test.
- 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.
- Hemoglobin ≥10 g/dl.
- Total bilirubin level ≤1.5 × ULN.
- +4 more criteria
You may not qualify if:
- Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of the first dose of BBI608.
- Major surgery within 4 weeks prior to first dose.
- 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.
- Pregnant or breastfeeding.
- Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent
- Unable or unwilling to swallow BBI608 capsules daily.
- Prior treatment with BBI608.
- Uncontrolled intercurrent illness
- For patients to be treated with a regimen containing 5-fluorouracil/leucovorin:
- Known hypersensitivity to 5-fluorouracil/leucovorin
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- For patients to be treated with a regimen containing capecitabine:
- Known hypersensitivity to capecitabine
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent
- +33 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Mayo Clinic Campus in Arizona
Phoenix, Arizona, 85054, United States
Florida Cancer Specialists
Fort Myers, Florida, 33916, United States
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
Indiana University Health Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Indiana University Health Arnett Hospital
Lafayette, Indiana, 47905, United States
Indiana University Health Ball Memorial Hospital
Muncie, Indiana, 47303, United States
Mayo Clinic
Rochester, Minnesota, 55901, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Institute for Translational Oncology Research, Greenville Health System
Greenville, South Carolina, 29605, United States
Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, 37203, United States
Ottawa Hospital Cancer Center
Ottawa, Ontario, K1H 8L6, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Tegan Nguyen
- Organization
- Sumitomo Dainippon Pharma Oncology
Study Officials
- STUDY DIRECTOR
Boston Biomedical
Sumitomo Pharma America, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2013
First Posted
December 31, 2013
Study Start
January 1, 2014
Primary Completion
March 1, 2019
Study Completion
November 1, 2019
Last Updated
November 15, 2023
Results First Posted
September 20, 2021
Record last verified: 2023-11