Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)

Phase 1

Completed

Brief Summary: The purpose of this research study is to determine the safety and efficacy of CPI-613 (devimistat) in the treatment of advanced biliary tract cancer when used in combination with standard of care chemotherapy (gemcitabine plus cisplatin) compared to gemcitabine plus cisplatin alone.

This research study has two parts:

In the phase 1 portion of this study, patients will receive a combination of CPI-613 and standard of care chemotherapy. Dose levels of CPI-613 will be adjusted to find the best dose, which will be the recommended phase 2 dose level.

In the phase 2 portion of this study, patients will be randomized into two arms. Patients in Arm A will receive the combination of the recommended dose level of CPI-613 and standard of care chemotherapy. Patients in Arm B will receive standard of care chemotherapy.

At the end of the study, researchers will compare the health outcomes of the patients that received CPI-613 + standard care to the outcomes of patients that received only standard care.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Phase 1 and Phase 2, Arm A (investigational)	CPI 613	On Day 1 and Day 8 of each 3-week cycle, patients will receive CPI-613 + gemcitabine and cisplatin. Patients may continue gemcitabine, cisplatin and CPI-613 for up to 2 years in absence of disease progression or unacceptable toxicity.
Phase 2, Arm B (standard of care)	Cisplatin	On Day 1 and Day 8 of each 3-week cycle, patients will receive gemcitabine and cisplatin. Patients may continue gemcitabine and cisplatin for up to 2 years in absence of disease progression or unacceptable toxicity.
Phase 1 and Phase 2, Arm A (investigational)	Cisplatin	On Day 1 and Day 8 of each 3-week cycle, patients will receive CPI-613 + gemcitabine and cisplatin. Patients may continue gemcitabine, cisplatin and CPI-613 for up to 2 years in absence of disease progression or unacceptable toxicity.
Phase 1 and Phase 2, Arm A (investigational)	Gemcitabine	On Day 1 and Day 8 of each 3-week cycle, patients will receive CPI-613 + gemcitabine and cisplatin. Patients may continue gemcitabine, cisplatin and CPI-613 for up to 2 years in absence of disease progression or unacceptable toxicity.
Phase 2, Arm B (standard of care)	Gemcitabine	On Day 1 and Day 8 of each 3-week cycle, patients will receive gemcitabine and cisplatin. Patients may continue gemcitabine and cisplatin for up to 2 years in absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Phase 1: Incidence of dose-limiting toxicity	Up to day 22	Dose limiting toxicities will determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of combination therapy with CPI-613 + gemcitabine and cisplatin. Assessed using the NCI CTCAE v5.0
Phase 2: Overall Response Rate (ORR)	Until last dose of study treatment (up to 2 years)	Objective response assessment will be determined by review of CT or MR scans of the chest, abdomen and pelvis. ORR (Partial Response + Complete Response) will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, during active study treatment. All enrolled patients who receive at least 1 cycle of therapy and have their disease re-evaluated will be considered evaluable for response. (Note: Patients who exhibit objective disease progression prior to the end of cycle 1 will also be considered evaluable.)

Secondary Outcome Measures

Name	Time	Method
Median Progression Free Survival (PFS)	Until last dose of study treatment (up to 2 years)	PFS will be determined from date of first study treatment until the date of radiological or clinical progression (leading to withdrawal from the study) or date of last disease evaluation (for patients without progression). It will be calculated using the product-limit method of Kaplan and Meier. All patients that receive at least one dose of study treatment will be considered evaluable.
Incidence of Toxicities	Up to 100 days after last dose of study treatment	To evaluate the safety of CPI-613 in combination with gemcitabine and cisplatin in this patient population, assessed using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0. All patients that receive at least one dose of study treatment will be considered evaluable.
Median Overall Survival (OS)	Up to 3 years after enrollment	From date of first study treatment until date of last disease evaluation or until death from any cause. Using the product-limit method of Kaplan and Meier.

Locations (10): Fred Hutch/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
University Hospitals - Seidman Cancer Center
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Cleveland, Ohio, United States
Northwestern University -- Lurie Comprehensive Cancer Center
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Chicago, Illinois, United States
Allegheny Health Network
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Pittsburgh, Pennsylvania, United States
University of Arizona Cancer Center
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Tucson, Arizona, United States
Atlantic Health System
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Morristown, New Jersey, United States
Vanderbilt-Ingram Cancer Center
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Nashville, Tennessee, United States
University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, United States
University of Texas Southwestern -- Simmons Comprehensive Cancer Center
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Dallas, Texas, United States
University of Wisconsin - Carbone Cancer Center
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Madison, Wisconsin, United States