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Advanced Gastrointestinal CancerPhase 1/2NCT02024607

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

A Phase 1/2 study testing BBI608, Fluorouracil and Oxaliplatin in people with Advanced Gastrointestinal Cancer, run by Sumitomo Pharma America, Inc. at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Gastrointestinal Cancer
What is being tested?
BBI608, Fluorouracil and Oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
495 participants
Where
15 sitesin 2 countries
Study dates
Jan 2014to Nov 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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).
  • Absolute neutrophil count ≥ 1.5 x 10^9/L.
  • Platelets ≥100 x 10^9/L.
  • Life expectancy estimated at ≥3 months.

Who cannot join

  • 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.
Show all 48Show fewer
  • 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
  • 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
  • For patients to be treated with a regimen containing irinotecan:
  • Known hypersensitivity to irinotecan
  • Abnormal glucuronidation of bilirubin
  • 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)
  • 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

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Tennessee Oncology - Chattanooga

    Chattanooga, Tennessee, 37404

  • Oncology Hematology Care, Inc.

    Cincinnati, Ohio, 45242

  • Florida Cancer Specialists

    Fort Myers, Florida, 33916

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Indiana University Health Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Institute for Translational Oncology Research, Greenville Health System

    Greenville, South Carolina, 29605

  • Indiana University Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Indiana University Health Arnett Hospital

    Lafayette, Indiana, 47905

  • Indiana University Health Ball Memorial Hospital

    Muncie, Indiana, 47303

  • Tennessee Oncology - Nashville

    Nashville, Tennessee, 37203

  • Mayo Clinic Campus in Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55901

Other trials in United States

Canada1 site

  • Ottawa Hospital Cancer Center

    Ottawa, Ontario, K1H 8L6

Other trials in Canada

About this study

Official title: A Phase Ib/II Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer

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.

Read the 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.

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02024607
Study groupRoleWhat they receive
ARM A- BBI608 in combination with FOLFOX6ExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin
ARM B- BBI608 in combination with FOLFOX6 and BevacizumabExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Bevacizumab
ARM C- BBI608 in combination with CAPOXExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Oxaliplatin; Drug: Capecitabine
ARM D- BBI608 in combination with FOLFIRIExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Fluorouracil; Drug: Leucovorin; Drug: Irinotecan
ARM E- BBI608 in combination with FOLFIRI and BevacizumabExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Fluorouracil; Drug: Leucovorin; Drug: Irinotecan; Drug: Bevacizumab
ARM F- BBI608 in combination with RegorafenibExperimentalBBI608 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.
Receives: Drug: BBI608; Drug: Regorafenib
Arm G- BBI608 in combination with IrinotecanExperimentalBBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m^2 will be administered intravenously. This regimen will be repeated every 14 days thereafter.
Receives: Drug: BBI608; Drug: Irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 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.

  2. 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.

    Measured: 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)

  1. 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.

    Measured: Blood samples drawn on days 1, 2, 15, 16, 21, and 22 of the first study cycle

  2. Pharmacodynamics

    To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin

    Measured: Day 1 of cycle 2

  3. 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.

    Measured: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months.

  4. 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.

    Measured: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

  5. 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.

    Measured: 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

  6. 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.

    Measured: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 36 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2013 (estimated)
  2. Study startJan 2014
  3. Primary completionMar 2019
  4. Study completionNov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
495 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02024607
Sponsor's protocol ID
BBI608-246
Status last verified
Nov 2023
First submitted
20 Dec 2013
Last updated
15 Nov 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BBI608, Fluorouracil and Oxaliplatin in people with Advanced Gastrointestinal Cancer, run by Sumitomo Pharma America, Inc. at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02024607.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2023.

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