A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer
A Phase Ib Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Metastatic Pancreatic Adenocarcinoma
2 other identifiers
interventional
139
1 country
12
Brief Summary
This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered in combination with Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2014
Longer than P75 for phase_1
12 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
Study Start
First participant enrolled
August 1, 2014
CompletedFirst Submitted
Initial submission to the registry
August 30, 2014
CompletedFirst Posted
Study publicly available on registry
September 4, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2020
CompletedNovember 18, 2023
April 1, 2022
5.8 years
August 30, 2014
November 13, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Safety by reporting the adverse events and serious adverse events
6 months
Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs)
3 months
Secondary Outcomes (4)
Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing tumor assessments every 8 weeks
6 months
Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing serum CA 19-9 level measurement
6 months
Assess pharmacokinetic profile of BBI608 when administered in combination with standard chemotherapies
On Day 1 and Day 15 of the first cycle prior to dosing and 1, 2, 3, 3.5, 4, 5, 5.5, 7, 8, 9, 10, 11 and 24 hours after first dose
Assess pharmacodynamic activity of BBI608 when administered in combination with standard chemotherapies
During the first 28 days of treatment
Study Arms (4)
A: BBI608 in combination with Gemcitabine and nab-Paclitaxel
EXPERIMENTALB: BBI608 in combination with modified FOLFIRINOX
EXPERIMENTALC: BBI608 in combination with FOLFIRI
EXPERIMENTALD: BBI608 in combination with MM-398, 5-FU and leucovorin
EXPERIMENTALInterventions
Administered continuously twice daily with doses separated by 12 hours
Nab-paclitaxel 125 mg/m\^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
Gemcitabine 1000 mg/m\^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
Oxaliplatin 85 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Arm C, D: Leucovorin 400 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Arm B: Irinotecan 165 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Irinotecan 165 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Arm B, D: Fluorouracil 2400 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m\^2 I.V. bolus followed by 2400 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
MM-398 70 mg/m\^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Eligibility Criteria
You may qualify if:
- Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP), the local regulatory requirements, and permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) prior to study-specific screening procedures.
- Patients must have histologic or cytologic evidence of adenocarcinoma of the pancreas, such as a core tissue biopsy or a surgical resection specimen.
- Patients must have metastatic disease. Baseline imaging of chest, abdomen and pelvis (CT or MRI) within 21 days prior to initiation of protocol therapy is required.
- Patients must have measurable disease as defined by RECIST 1.1.
- Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.
- Patients enrolling onto Arm A (Gemcitabine and nab-Paclitaxel) or Arm B (mFOLFIRINOX) are allowed to have up to two prior lines of systemic therapy, with adjuvant therapy counted as one line of therapy as long as disease recurrence occurred \> 6 months of last dose of therapy. Prior systemic therapy in the metastatic setting is allowed for as long as the therapy contained BBI608 in combination with either Gemcitabine and nab-Paclitaxel or mFOLFIRINOX. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible.
- Patients who received Gemcitabine-based therapy in an adjuvant setting will be allowed to be enrolled on Arm A of the trial (Gemcitabine with nab-Paclitaxel) as long as their last Gemcitabine administration was at least 6 months prior to the first dose of BBI608.
- Patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) are allowed to have prior mFOLFIRINOX in combination with BBI608 in the metastatic setting.
- Patients enrolling onto Arm B (mFOLFIRINOX) are allowed to have prior Gemcitabine with nab-Paclitaxel in combination with BBI608 in the metastatic setting.
- Prior treatment with radiotherapy is allowed.
- Patients enrolling onto Arm C (FOLFIRI) or Arm D (MM-398 with 5-FU and leucovorin) must have failed one prior line of gemcitabine-based therapy with or without BBI608 in the metastatic setting. No additional lines of therapy in the metastatic setting are allowed. Prior adjuvant therapy with gemcitabine is allowed as long as disease recurrence occurred \> 6 months of last dose of therapy. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible. Prior treatment with radiotherapy is allowed.
- ≥ 18 years of age.
- Patients must have an ECOG Performance Status ≤ 1.
- 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 (preceding 72 hours of first day of BBI608 treatment).
- +13 more criteria
You may not qualify if:
- Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 14 days of the first dose of BBI608, except for BBI608 for which a washout period is not required.
- Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days since last receiving anti-cancer treatment which did not include BBI608, provided that all treatment-related adverse events have resolved or have been deemed irreversible (except for alopecia).
- Patients who previously received BBI608 for treatment of PDAC on the BBI608-118 (BBI608-201PANC) study may continue with BBI608 in monotherapy between discontinuation of the first chemotherapy backbone and start of the second chemotherapy backbone. Patients may begin chemotherapy backbone on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days and a maximum of 30 days since last receiving anti-cancer treatment which included BBI608, provided that all treatment-related adverse events have resolved or have been deemed irreversible (except for alopecia).
- Patients with neuroendocrine neoplasms will be excluded.
- Major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to first dose.
- Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable.
- History of posterior reversible encephalopathy syndrome.
- Neurosensory neuropathy ≥ grade 2 at baseline.
- Pregnant or breastfeeding.
- Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection and small intestinal resection).
- Unable or unwilling to swallow BBI608 capsules daily.
- Uncontrolled chronic diarrhea ≥ grade 2 at baseline.
- Uncontrolled intercurrent illness including, but not limited to uncontrolled active infection (including bacterial, viral or fungal requiring systemic therapy), clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
- History of other active malignancies.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Mayo Clinic Arizona
Phoenix, Arizona, 85054, 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 Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, 89014, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
The University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Texas Oncology - Austin Midtown
Austin, Texas, 78705, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Texas Oncology - SAT&BC
San Antonio, Texas, 78216, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2014
First Posted
September 4, 2014
Study Start
August 1, 2014
Primary Completion
June 1, 2020
Study Completion
June 1, 2020
Last Updated
November 18, 2023
Record last verified: 2022-04