Clinical Trials /

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

NCT04203160

Description:

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.

Related Conditions:
  • Biliary Tract Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)
  • Official Title: A Multi-Center Randomized Phase IB/II Study of Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2019.116
  • SECONDARY ID: HUM00170490
  • NCT ID: NCT04203160

Conditions

  • Biliary Tract Cancer

Interventions

DrugSynonymsArms
CPI 613Devimistat®Phase 1 and Phase 2, Arm A (investigational)
GemcitabineGemzar®Phase 1 and Phase 2, Arm A (investigational)
CisplatinCDDP, Platinol®, NSC-119875Phase 1 and Phase 2, Arm A (investigational)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1 and Phase 2, Arm A (investigational)ExperimentalOn 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.
  • CPI 613
  • Gemcitabine
  • Cisplatin
Phase 2, Arm B (standard of care)Active ComparatorOn 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.
  • Gemcitabine
  • Cisplatin

Eligibility Criteria

        Inclusion:

          -  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 histology are excluded.

          -  Patients may not have received prior systemic treatment (chemotherapy or targeted
             therapy) for advanced BTC. Prior adjuvant 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.

          -  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.

        Exclusions:

          -  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 non-melanoma skin cancer or cervical carcinoma in
             situ). Patients with history of 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) .

          -  Psychiatric illness, other significant medical illness, or social situation which, in
             the investigator's opinion, would limit compliance or ability to comply with study
             requirements.

          -  Pregnancy or breastfeeding. (Women must not be pregnant or breastfeeding since study
             drugs may harm the fetus or child. All females of childbearing potential [not
             surgically sterilized and between menarche and 1 year post menopause] must have a
             negative screening pregnancy test.)

          -  Active heart disease including symptomatic heart failure (NYHA class 3 or 4), unstable
             angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease.

          -  Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for
             treatment of either a psychiatric or physical (e.g. infectious disease) illness would
             be excluded.

          -  Prolonged QTcF interval >480 msec.

          -  Known hypersensitivity to cisplatin, gemcitabine or CPI-613, or its inactive
             components.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Incidence of dose-limiting toxicity
Time Frame:Up to day 22
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Median Progression Free Survival (PFS)
Time Frame:Until last dose of study treatment (up to 2 years)
Safety Issue:
Description: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.
Measure:Median Overall Survival (OS)
Time Frame:Up to 3 years after enrollment
Safety Issue:
Description: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.
Measure:Incidence of Toxicities
Time Frame:Up to 100 days after last dose of study treatment
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Trial Keywords

  • Cholangiocarcinoma
  • Gallbladder cancer

Last Updated

December 18, 2019