NCT04203160

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

Terminated Phase 1, PHASE2 Results posted Last updated 31 December 2025

What this trial tests

Phase 1, PHASE2 trial testing CPI 613 in Biliary Tract Cancer in 75 participants. Terminated before completion.

Timeline

23 June 2020

Primary endpoint
16 April 2024

29 April 2024

Quick facts

Lead sponsor	University of Michigan Rogel Cancer Center
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	75
Start date	23 June 2020
Primary completion	16 April 2024
Estimated completion	29 April 2024
Sites	10 locations across United States

Drugs / interventions tested

• CPI 613 — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →
• Cisplatin (cisplatin) — full drug profile →

Conditions studied

• Biliary Tract Cancer — all drugs for Biliary Tract Cancer →

Sponsor

University of Michigan Rogel Cancer Center

Who can join

18 and older, any sex, with Biliary Tract Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1: Incidence of Dose-limiting Toxicity Primary · 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

Group	Value	95% CI
Phase 2, Arm A (Investigational)	0
Phase 2, Arm B (Standard of Care)	0
Phase 1, CPI-613 500 mg/m2	0
Phase 1, CPI-613 1000 mg/m2	0
Phase 1, CPI-613 1500 mg/m2	0
Phase 1, CPI-613 2000 mg/m2	1

Phase 2: Overall Response Rate (ORR) Primary · 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.)

Group	Value	95% CI
Phase 2, Arm A (Investigational)	15
Phase 2, Arm B (Standard of Care)	6
Phase 1, CPI-613 500 mg/m2	0
Phase 1, CPI-613 1000 mg/m2	0
Phase 1, CPI-613 1500 mg/m2	0
Phase 1, CPI-613 2000 mg/m2	0

Median Progression Free Survival (PFS) Secondary · 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.

Group	Value	95% CI
Phase 2, Arm A (Investigational)	8.7	5.8 – 11.3
Phase 2, Arm B (Standard of Care)	9.6	7.3 – NA

Median Overall Survival (OS) Secondary · 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.

Group	Value	95% CI
Phase 2, Arm A (Investigational)	15.6	11.8 – 22.5
Phase 2, Arm B (Standard of Care)	22.2	8.6 – NA

Incidence of Toxicities Secondary · 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. Number of patients experiencing the maximum graded toxicity (Grade 2 or higher).

Abdominal pain- Grade 3

Group	Value	95% CI
Phase 2, Arm A (Investigational)	1
Phase 2, Arm B (Standard of Care)	0

Alanine aminotransferase increased- Grade 2

Group	Value	95% CI
Phase 2, Arm A (Investigational)	1
Phase 2, Arm B (Standard of Care)	0

Alopecia- Grade 2

Group	Value	95% CI
Phase 2, Arm A (Investigational)	2
Phase 2, Arm B (Standard of Care)	1

Anemia- Grade 2

Group	Value	95% CI
Phase 2, Arm A (Investigational)	4
Phase 2, Arm B (Standard of Care)	2

Anemia- Grade 3

Group	Value	95% CI
Phase 2, Arm A (Investigational)	10
Phase 2, Arm B (Standard of Care)	7

Anorexia- Grade 2

Group	Value	95% CI
Phase 2, Arm A (Investigational)	3
Phase 2, Arm B (Standard of Care)	4

Anorexia- Grade 3

Group	Value	95% CI
Phase 2, Arm A (Investigational)	1
Phase 2, Arm B (Standard of Care)	0

Aspartate aminotransferase increased- Grade 2

Group	Value	95% CI
Phase 2, Arm A (Investigational)	1
Phase 2, Arm B (Standard of Care)	0

Adverse events — posted to ClinicalTrials.gov

Time frame: All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 2 years. All-Cause Mortality monitored/assessed up to 3 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 2, Arm A (Investigational)

Serious: 13/37 (35%)

Deaths: 25/37

Phase 2, Arm B (Standard of Care)

Serious: 9/18 (50%)

Deaths: 7/18

Phase 1, CPI-613 500 mg/m2

Serious: 0/1 (0%)

Deaths: 0/1

Phase 1, CPI-613 1000 mg/m2

Serious: 1/1 (100%)

Deaths: 1/1

Phase 1, CPI-613 1500 mg/m2

Serious: 2/2 (100%)

Deaths: 2/2

Phase 1, CPI-613 2000 mg/m2

Serious: 11/16 (69%)

Deaths: 12/16

Serious adverse events (49 terms)

Reaction	System	Phase 2, Arm A (Investigat…	Phase 2, Arm B (Standard o…	Phase 1, CPI-613 500 mg/m2	Phase 1, CPI-613 1000 mg/m2	Phase 1, CPI-613 1500 mg/m2	Phase 1, CPI-613 2000 mg/m2
Sepsis	Infections and infestations	—	—	—	—	—	—
Biliary tract infection	Gastrointestinal disorders	—	—	—	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—	—	—
Febrile neutropenia	Injury, poisoning and procedural complications	—	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—	—
Stroke	Nervous system disorders	—	—	—	—	—	—
Thromboembolic event	Vascular disorders	—	—	—	—	—	—
Progressive Disease	General disorders	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—
Bile duct stenosis	Gastrointestinal disorders	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—
Colonic obstruction	Gastrointestinal disorders	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—
Enterocolitis infectious	Infections and infestations	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Transient ischemic attacks	Nervous system disorders	—	—	—	—	—	—
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Vertigo	General disorders	—	—	—	—	—	—
Anemia	Investigations	—	—	—	—	—	—

Other adverse events (165 terms — click to expand)

Reaction	System	Phase 2, Arm A (Investigat…	Phase 2, Arm B (Standard o…	Phase 1, CPI-613 500 mg/m2	Phase 1, CPI-613 1000 mg/m2	Phase 1, CPI-613 1500 mg/m2	Phase 1, CPI-613 2000 mg/m2
Fatigue	General disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—
Anemia	Investigations	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Anorexia	General disorders	—	—	—	—	—	—
Hypomagnesemia	Investigations	—	—	—	—	—	—
Dizziness	General disorders	—	—	—	—	—	—
Dysgeusia	Gastrointestinal disorders	—	—	—	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—
Alopecia	General disorders	—	—	—	—	—	—
Back pain	General disorders	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—
Edema limbs	General disorders	—	—	—	—	—	—
Generalized muscle weakness	General disorders	—	—	—	—	—	—
Hypokalemia	Investigations	—	—	—	—	—	—
Infusion related reaction	Infections and infestations	—	—	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Biliary tract infection	Infections and infestations	—	—	—	—	—	—
Blurred vision	Eye disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Creatinine increased	Investigations	—	—	—	—	—	—
Dysuria	Renal and urinary disorders	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—
Headache	General disorders	—	—	—	—	—	—
Hiccups	General disorders	—	—	—	—	—	—
Hyperglycemia	Investigations	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Mucositis oral	General disorders	—	—	—	—	—	—
Thromboembolic event	General disorders	—	—	—	—	—	—

Most-reported serious reactions: Sepsis, Biliary tract infection, Pancreatitis, Abdominal pain, Cholecystitis, Febrile neutropenia, Lung infection, Stroke.

Data from ClinicalTrials.gov NCT04203160 adverse events section.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.
   Jin P, Jiang J, Zhou L, Huang Z, et al · · 2022 · cited 180× · PMID 35851420 · DOI 10.1186/s13045-022-01313-4
2. Overview of current targeted therapy in gallbladder cancer.
   Song X, Hu Y, Li Y, Shao R, et al · · 2020 · cited 123× · PMID 33028805 · DOI 10.1038/s41392-020-00324-2
3. Cancer metabolism and carcinogenesis.
   Yang J, Shay C, Saba NF, Teng Y. · · 2024 · cited 73× · PMID 38287402 · DOI 10.1186/s40164-024-00482-x
4. Druggability of lipid metabolism modulation against renal fibrosis.
   Chen YY, Chen XG, Zhang S. · · 2022 · cited 43× · PMID 33990764 · DOI 10.1038/s41401-021-00660-1
5. Gallbladder cancer: current and future treatment options.
   Zhou Y, Yuan K, Yang Y, Ji Z, et al · · 2023 · cited 40× · PMID 37251319 · DOI 10.3389/fphar.2023.1183619
6. Targeting mitochondrial quality control: new therapeutic strategies for major diseases.
   Hong WL, Huang H, Zeng X, Duan CY. · · 2024 · cited 38× · PMID 39164792 · DOI 10.1186/s40779-024-00556-1
7. Targeting 2-oxoglutarate dehydrogenase for cancer treatment.
   Chang LC, Chiang SK, Chen SE, Hung MC. · · 2022 · cited 31× · PMID 35530286
8. Devimistat in Combination with Gemcitabine and Cisplatin in Biliary Tract Cancer: Preclinical Evaluation and Phase Ib Multicenter Clinical Trial (BilT-04).
   Mohan A, Griffith KA, Wuchu F, Zhen DB, et al · · 2023 · cited 20× · PMID 37115501 · DOI 10.1158/1078-0432.ccr-23-0036