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

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 13-007530
    • Rochester, Minnesota: 13-007530
  • NCT ID:

    NCT02024607
  • Sponsor Protocol Number:

    BBI608-246

About this study

This is an open label, multi-center, Phase Ib 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. 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. A histologically confirmed solid tumor of the gastrointestinal tract including
    • Advanced unresectable, metastatic or recurrent colorectal carcinoma 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. Patients with colorectal carcinoma 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 or CAPOX 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, or FOLFIRI 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% (Appendix E).
  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 m2 for patients with creatinine levels above institutional normal (as determined by Cockcroft-Gault equation).
  12. Absolute neutrophil count ≥ 1.5 x 109/L.
  13. Platelets ≥100 x 109/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:
    • Known hypersensitivity to 5-fluorouracil/leucovorin
    • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  10. 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
  11. For patients to be treated with a regimen containing oxaliplatin:
    • Neurosensory neuropathy ≥ grade 2 at baseline
    • Known hypersensitivity to oxaliplatin or other platinum containing compounds
  12. For patients to be treated with a regimen containing irinotecan:
    • Known hypersensitivity to irinotecan
    • Abnormal glucuronidation of bilirubin
  13. For patients to be treated with a regimen containing bevacizumab:
    • Current uncontrolled hypertension as well as prior history of hypertensive crisis or hypertensive encephalopathy
    • 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
    • History of arterial thrombotic or embolic events (within 6 months prior to study entry)
    • Significant vascular disease
    • Evidence of bleeding diathesis or clinically significant coagulopathy
    • 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
    • Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥ 2+.
    • History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months
    • Ongoing serious, non-healing wound, ulcer, or bone fracture
    • Known hypersensitivity to any component of bevacizumab
    • History of reversible posterior leukoencephalopathy syndrome (RPLS)
  14. For patients to be treated with a regimen containing regorafenib:
    • 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
    • Current uncontrolled hypertension
    • Interstitial lung disease with ongoing signs and symptoms at the time of screening
    • History of HIV infection or chronic hepatitis B or C Active clinically serious infections
    • History of arterial or embolic events (within 6 months prior to study entry)
    • Liver cirrhosis ≥ Child-Pugh class B with uncontrolled ascites
    • History of RPLS
    • Ongoing serious, non-healing wound, ulcer, or bone fracture
    • Evidence of bleeding diathesis or a clinically significant coagulopathy
    • Renal failure requiring hemo- or peritoneal dialysis
    • Persistent proteinuria of CTCAE grade 3 (>3.5g/24 hours)
    • Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent
    • Known hypersensitivity to regorafenib

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Joleen Hubbard, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Joleen Hubbard, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015