A Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT02279719
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is an open label, three-arm, phase 1 dose escalation study and phase 2 study of BBI608 in combination with sorafenib, or BBI503 in combination with sorafenib. The study population is adult patients with advanced hepatocellular carcinoma who have not received systemic chemotherapy.
- Detailed Description
This is an open label, three-arm, phase 1 dose escalation study and phase 2 study of BBI608 in combination with sorafenib, or BBI503 in combination with sorafenib. The study population is adult patients with advanced hepatocellular carcinoma (HCC) who have not received systemic chemotherapy.
The phase 1 portion will involve dose-escalation of BBI608 administered in combination with a fixed starting dose of sorafenib (Arm 1), and dose escalation of BBI503 administered in combination with a fixed starting dose of sorafenib (Arm 2). The fixed starting dose-level of sorafenib for both arms will be 400 mg twice daily (800 mg total daily dose). Eligible patients will be randomized to either Arm 1 or Arm 2.
The phase 2 portion will be an open-label, 3-arm, randomized trial of patients with advanced HCC who have not received prior systemic treatment. Patients will be randomized to receive either, Arm 1: sorafenib administered in combination with BBI608 (at the RP2D determined for BBI608 plus sorafenib during the phase 1 portion); Arm 2: sorafenib in combination with BBI503 (at the RP2D determined for BBI503 plus sorafenib during the phase 1 portion), or Arm 3: sorafenib alone at a starting dose of 400 mg twice daily. The starting dose for sorafenib is the same for all study arms.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BBI608 and Sorafenib BBI608 - BBI503 and Sorafenib BBI503 - BBI608 and Sorafenib Sorafenib - BBI503 and Sorafenib Sorafenib - Sorafenib Sorafenib -
- Primary Outcome Measures
Name Time Method To Assess the Number of Patients Who Experienced Adverse Events for Phase IB. Adverse events will be assessed at baseline, while the participant is taking drugs, and for 30 days after stopping therapy. It was expected that patients would receive between 4-24 weeks treatment. Assessment of safety of either BBI608 or BBI503 given in combination with sorafenib to patients with hepatocellular carcinoma by reporting of adverse events and serious adverse events
Assessment of the Dose Limiting Toxicities for the Napabucasin and Amcasertib Arm in Combination With Sorafenib for Phase IB 16 weeks including 2-week Sorafenib run-in period prior to initiation of combination therapy To assess the dose limiting toxicities for phase IB
Determination of the Recommended Phase II Dose for Napabucasin and Amcasertib Arm in Combination With Sorafenib 16 weeks including 2-week Sorafenib run-in period prior to initiation of combination therapy To determine the recommended phase II dose for Napabucasin and Amcasertib arm in combination with sorafenib
Assessment of Disease Control Rate in the Intent to Treat Population- Phase II Assessment of the preliminary anti-tumor activity by performing tumor assessments at baseline and every 8 weeks after the date of the first dose of protocol therapy To evaluate the preliminary anti-tumor activity in patients with advanced hepatocellular carcinoma randomized to receive treatment with sorafenib in combination with Napabucasin, sorafenib in combination with Amcasertib\*, or sorafenib alone; Napabucasin and Amcasertib will be administered at their respective RP2D dose levels for combination administration with sorafenib, which were determined during the phase Ib portion of the study.
The radiologic assessments will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST for patients with hepatocellular carcinoma.
Disease control rate (DCR), defined as the proportion of patients with best response of complete response (CR), Partial Response (PR), or stable disease (SD)Assessment of Objective Response Rate in the Intent to Treat Population - Phase II Assessment of the preliminary anti-tumor activity by performing tumor assessments at baseline and every 8 weeks after the date of the first dose of protocol therapy To evaluate the preliminary anti-tumor activity in patients with advanced hepatocellular carcinoma randomized to receive treatment with sorafenib in combination with Napabucasin or sorafenib in combination with Amcasertib, or sorafenib alone; Napabucasin and Amcasertib will be administered at their respective RP2D dose levels for combination administration with sorafenib, which were determined during the phase Ib portion of the study.
The radiologic assessments will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST for patients with hepatocellular carcinoma.
ORR was defined as the percentage of patients with a best overall response (BOR) of complete response (CR) or partial response (PR), using both RECIST and mRECIST assessment data.
- Secondary Outcome Measures
Name Time Method Assessment of the Pharmacodynamic Studies as Well as the Concentration of Study Drug (Either Napabucasin or Amcasertib) in Tumors On day 15 of the second cycle To perform biomarker studies for napabucasin administered in combination with sorafenib and for amcasertib administered in combination with sorafenib.
Assessment of the Pharmacokinetic Profile (Maximum Plasma Concentration and Area Under the Curve) of Either Napabucasin or Amcasertib. On Day 15 of the first cycle and Day 15 of the second cycle, prior to dosing and every one hours to 11 hours and 24 hours after first dose To determine the pharmacokinetic (PK) profile of napabucasin administered in combination with sorafenib and of amcasertib administered in combination with sorafenib.
Trial Locations
- Locations (29)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Piedmont Cancer Institute, P.C.
🇺🇸Atlanta, Georgia, United States
Drexel University
🇺🇸Philadelphia, Pennsylvania, United States
Baptist Health Medical Group Oncology, LLC
🇺🇸Miami, Florida, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Southern California Research Center
🇺🇸Coronado, California, United States
The Valley Hospital Luckow Pavilion
🇺🇸Paramus, New Jersey, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
USOR - Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
California Center Associates for Research and Excellence, Inc. (Ccare)
🇺🇸Encinitas, California, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
USOR - Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Kansas City Research Institure
🇺🇸Kansas City, Missouri, United States
USOR - New York Oncology Hematology
🇺🇸Albany, New York, United States
Carolinas Health Care System
🇺🇸Charlotte, North Carolina, United States
University of Rochester, Wilmot Cancer Institute
🇺🇸Rochester, New York, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati, Vontz Center
🇺🇸Cincinnati, Ohio, United States
USOR - Texas Oncology, Fort Worth 12th Ave
🇺🇸Fort Worth, Texas, United States
Texas Oncology - El Paso Cancer Treatment Center Joe Battle
🇺🇸El Paso, Texas, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
USOR - Texas Oncology, Tyler
🇺🇸Tyler, Texas, United States
Texas Oncology-McAllen South Second Street
🇺🇸McAllen, Texas, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
USOR - Texas Oncology, Austin Midtown
🇺🇸Austin, Texas, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States