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

NCT04203160 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: UMCC 2019.116HUM00170490
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 10

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.

Conditions

Biliary Tract Cancer

Keywords

Cholangiocarcinoma; Gallbladder cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1: Incidence of Dose-limiting Toxicity

  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

  Up to day 22

• Phase 2: Overall Response Rate (ORR)

  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.)

  Until last dose of study treatment (up to 2 years)

Secondary Outcomes (3)

• Median Progression Free Survival (PFS)

  Until last dose of study treatment (up to 2 years)

• Median Overall Survival (OS)

  Up to 3 years after enrollment

• Incidence of Toxicities

  Up to 100 days after last dose of study treatment

Study Arms (2)

Phase 1 and Phase 2, Arm A (investigational)

EXPERIMENTAL

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.

Drug: CPI 613; Drug: Gemcitabine; Drug: Cisplatin

Phase 2, Arm B (standard of care)

ACTIVE COMPARATOR

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.

Drug: Gemcitabine; Drug: Cisplatin

Interventions

CPI 613 DRUG

Given intravenously

Also known as: Devimistat®

Phase 1 and Phase 2, Arm A (investigational)

Gemcitabine DRUG

Given intravenously

Also known as: Gemzar®

Phase 1 and Phase 2, Arm A (investigational); Phase 2, Arm B (standard of care)

Cisplatin DRUG

Given intravenously

Also known as: CDDP, Platinol®, NSC-119875

Phase 1 and Phase 2, Arm A (investigational); Phase 2, Arm B (standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a pathologically or cytologically confirmed carcinoma (except neuroendocrine) of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gallbladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded.
• Patients may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC. Prior peri-operative chemotherapy is permitted provided it was completed \> 6 months from enrollment.
• Patients may have received prior radiation, chemoembolization, radioembolization or other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity. Extrahepatic palliative radiation is permitted if completed ≥ 2 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity
• Patients must have radiographically measurable disease (as per RECISTv1.1) in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site.
• Must be ≥ 18 years of age.
• Must have an ECOG performance status of 0-1.
• Ability to understand and willingness to sign IRB-approved informed consent.
• Willing to provide archived tissue, if available, from a previous diagnostic biopsy or surgery.
• Must be able to tolerate CT and/or MRI with contrast.
• Adequate organ function (per protocol) obtained ≤ 2 weeks prior to enrollment.
• Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation and for 6 months (for men and women) following completion of study therapy.
• Prior history of brain metastasis (unless previously treated, asymptomatic and stable for at least 3 months) or organ transplant.
• Underwent a major surgical procedure \< 4 weeks prior to enrollment.
• Active second malignancy other than in situ cancer or localized prostate cancer (Gleason score \<8). Patients with history of other malignancy are eligible provided primary treatment of that cancer was completed \> 1 year prior to enrollment and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy.
• Ongoing active, uncontrolled infection (must be afebrile for \> 48 hours off antibiotics) .

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (10)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Northwestern University -- Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

University Hospitals - Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern -- Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

devimistat; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Vaibhav Sahai, MBBS, MS

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II: 2:1 Randomization with Bayesian Design Control Arm

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 18, 2019
• Study Start: June 23, 2020
• Primary Completion: April 16, 2024
• Study Completion: April 29, 2024
• Last Updated: December 31, 2025
• Results First Posted: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)