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

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ClinicalTrials.gov Identifier: NCT04203160
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : May 25, 2022
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.


Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: CPI 613 Drug: Gemcitabine Drug: Cisplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase II: 2:1 Randomization with Bayesian Design Control Arm
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 23, 2020
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2025


Arm Intervention/treatment
Experimental: Phase 1 and Phase 2, Arm A (investigational)
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
Given intravenously
Other Name: Devimistat®

Drug: Gemcitabine
Given intravenously
Other Name: Gemzar®

Drug: Cisplatin
Given intravenously
Other Name: CDDP, Platinol®, NSC-119875

Active Comparator: Phase 2, Arm B (standard of care)
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
Given intravenously
Other Name: Gemzar®

Drug: Cisplatin
Given intravenously
Other Name: CDDP, Platinol®, NSC-119875




Primary Outcome Measures :
  1. Phase 1: Incidence of dose-limiting toxicity [ Time Frame: 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

  2. Phase 2: Overall Response Rate (ORR) [ Time Frame: 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 :
  1. Median Progression Free Survival (PFS) [ Time Frame: 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.

  2. Median Overall Survival (OS) [ Time Frame: 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.

  3. Incidence of Toxicities [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.
  • 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 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) .
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04203160


Locations
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United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Rachna Shroff, M.D.    520-626-4175    rshroff@arizona.edu   
Principal Investigator: Rachna Shroff, M.D.         
United States, Illinois
Northwestern University -- Lurie Comprehensive Cancer Center Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Lurie Cancer Center    312-695-1102    cancertrials@northwestern.edu   
Principal Investigator: Devalingam Mahalingam, MBBChBAO         
United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cancer AnswerLine    800-865-1125    CancerAnswerLine@med.umich.edu   
Principal Investigator: Vaibhav Sahai, MBBS, MS         
United States, New Jersey
Atlantic Health System Recruiting
Morristown, New Jersey, United States, 07960
Contact: Atlantic Hematology Oncology    973-971-7960      
Contact: Angela Alistar, MD       Angela.Alistar@atlantichealth.org   
Principal Investigator: Angela Alistar, M.D.         
United States, Ohio
University Hospitals - Seidman Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: UH Seidman CC    216-910-6304    david.bajor@UHhospitals.org   
Principal Investigator: David Bajor, M.D.         
United States, Pennsylvania
Allegheny Health Network Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Nathan Bahary    412-864-7764    Nathan.Bahary@ahn.org   
Principal Investigator: Nathan Bahary, MD, PhD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Laura Goff, M.D.    877-936-8422    laura.goff@vumc.org   
Principal Investigator: Laura Goff, M.D.         
United States, Texas
University of Texas Southwestern -- Simmons Comprehensive Cancer Center Recruiting
Dallas, Texas, United States, 75390
Contact: David Hsiesh, M.D.    214-645-8300    Muhammad.Beg@UTSouthwestern.edu   
Contact    214-648-1996    david.hsieh@utsouthwestern.edu   
Principal Investigator: David Hsiesh, M.D.         
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: David Zhen, M.D.    206-606-1743    dbzhen@uw.edu   
Principal Investigator: David Zhen, M.D.         
United States, Wisconsin
University of Wisconsin - Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53705
Contact: Dustin Deming, M.D.    608-265-1042    ddeming@medicine.wisc.edu   
Principal Investigator: Dustin Deming, M.D.         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Vaibhav Sahai, MBBS, MS University of Michigan Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT04203160    
Other Study ID Numbers: UMCC 2019.116
HUM00170490 ( Other Identifier: University of Michigan )
First Posted: December 18, 2019    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Michigan Rogel Cancer Center:
Cholangiocarcinoma
Gallbladder cancer
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs