Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02024607
Recruitment Status : Active, not recruiting
First Posted : December 31, 2013
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc

Tracking Information
First Submitted Date  ICMJE December 20, 2013
First Posted Date  ICMJE December 31, 2013
Last Update Posted Date March 27, 2019
Study Start Date  ICMJE January 2014
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events will be assessed at baseline, while the participant is taking BBI608, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 4 months. ]
    Assessment of safety of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan to patients with advanced gastrointestinal malignancies by reporting of adverse events and serious adverse events
  • To assess the objective response rate (ORR) of BBI608 administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer (mCRC) [ Time Frame: Anti-tumor activity, including ORR, is assessed every 8 weeks, from the first dose of BBI608 to 30 days after the last dose of BBI608. ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 26, 2013)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events will be assessed at baseline, while the participant is taking BBI608, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 4 months. ]
Assessment of safety of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib to patients with advanced gastrointestinal malignancies by reporting of adverse events and serious adverse events
Change History Complete list of historical versions of study NCT02024607 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • Pharmacokinetic profile of BBI608 assessed by maximum plasma concentration and area under the curve [ Time Frame: During the first 28 days of treatment ]
    Blood sampling to assess the pharmacokinetic profile of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib.
  • Pharmacodynamic activity assessed by tumor biopsy [ Time Frame: During the first 28 days of treatment ]
    Tumor Biopsy(s) to provide information on analysis of the targets and downstream genes/ effect of BBI608 on cancer stem cells through immunohistochemistry.
  • Anti-tumor activity by performing tumor assessments every 8 weeks [ Time Frame: Anti-tumor activity is assessed every 8 weeks, from the first dose of BBI608 to 30 days after the last dose of BBI608, an expected average of 5 months ]
    To assess the preliminary anti-tumor activity of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan.
  • To assess the disease control rate (DCR), progression free survival (PFS) and overall survival (OS) of BBI608 administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory mCRC [ Time Frame: Anti-tumor activity, including DCR and PFS, is assessed every 8 weeks, from the first dose of BBI608 to 30 days after the last dose of BBI608. Patients are followed for OS until death or withdrawal of consent to OS follow-up. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 26, 2013)
  • Assess pharmacokinetic profile [ Time Frame: During the first 28 days of treatment ]
    Blood sampling to assess the pharmacokinetic profile of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib.
  • Assess pharmacodynamic activity [ Time Frame: During the first 28 days of treatment ]
    Tumor Biopsy(s) to provide information on analysis of the targets and downstream genes/ effect of BBI608 on cancer stem cells through immunohistochemistry.
  • Anti-tumor activity [ Time Frame: Anti-tumor activity is assessed every 8 weeks, from the first dose of BBI608 to 30 days after the last dose of BBI608, an expected average of 5 months ]
    To assess the preliminary anti-tumor activity of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer
Official Title  ICMJE A Phase Ib/II Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Gastrointestinal Cancer
Intervention  ICMJE
  • Drug: BBI608
    Other Names:
    • Napabucasin
    • BB608
    • BBI-608
  • Drug: Fluorouracil
    Other Names:
    • 5-FU
    • Carac
    • Efudex
    • Fluoroplex
    • Adrucil
  • Drug: Oxaliplatin
    Other Name: Eloxatin
  • Drug: Leucovorin
    Other Name: Folinic Acid
  • Drug: Irinotecan
    Other Name: Camptosar
  • Drug: Bevacizumab
    Other Name: Avastin
  • Drug: Capecitabine
    Other Name: Xeloda
  • Drug: Regorafenib
    Other Name: Stivarga
Study Arms  ICMJE
  • Experimental: ARM A- BBI608 in combination with FOLFOX6
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Fluorouracil
    • Drug: Oxaliplatin
    • Drug: Leucovorin
  • Experimental: ARM B- BBI608 in combination with FOLFOX6 and Bevacizumab
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Fluorouracil
    • Drug: Oxaliplatin
    • Drug: Leucovorin
    • Drug: Bevacizumab
  • Experimental: ARM C- BBI608 in combination with CAPOX
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Oxaliplatin
    • Drug: Capecitabine
  • Experimental: ARM D- BBI608 in combination with FOLFIRI
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Fluorouracil
    • Drug: Leucovorin
    • Drug: Irinotecan
  • Experimental: ARM E- BBI608 in combination with FOLFIRI and Bevacizumab
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Fluorouracil
    • Drug: Leucovorin
    • Drug: Irinotecan
    • Drug: Bevacizumab
  • Experimental: ARM F- BBI608 in combination with Regorafenib
    BBI608 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.
    Interventions:
    • Drug: BBI608
    • Drug: Regorafenib
  • Experimental: Arm G- BBI608 in combination with Irinotecan
    BBI608 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:
    • Drug: BBI608
    • Drug: Irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 12, 2018)
495
Original Estimated Enrollment  ICMJE
 (submitted: December 26, 2013)
144
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02024607
Other Study ID Numbers  ICMJE BBI608-246
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boston Biomedical, Inc
Study Sponsor  ICMJE Boston Biomedical, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Boston Biomedical Boston Biomedical, Inc
PRS Account Boston Biomedical, Inc
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP