NCT05325281

CPI-613 (Devimistat) in Combination With Chemoradiation in Patients With Pancreatic Adenocarcinoma

A Phase I Dose-Escalation Study of CPI-613 (Devimistat) in Combination With Chemoradiation in Patients With Pancreatic Adenocarcinoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, open-label, phase I study designed to determine the maximum tolerated dose (MTD) and safety profile of CPI-613® when used concomitantly with chemoradiation for local control of pancreatic adenocarcinoma (PDAC).

Detailed description

This study is designed to test the hypothesis that a combination of gemcitabine and radiation therapy (Gem-RT) with CPI-613®, a selective mitochondrial metabolism inhibitor in PDAC tumor cells, will be well tolerated without additional significant toxicity. Additionally, CPI-613® is expected to improve the Gem-RT effectiveness, resulting in durable local control of disease. As a necessary and initial step to translate preclinical observations into a patient setting and test our proposed hypotheses, the investigators will perform a dose-finding phase I clinical trial that has been designed to evaluate the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profile of CPI-613® along with standard of care Gem-RT in patients with unresectable PDAC in need of definitive local control of disease. The overarching goals for this trial are to determine the safety and toxicity of CPI-613® when given concurrently with Gem-RT.

Conditions

• Pancreas Adenocarcinoma

Interventions

Type	Name	Description
DRUG	CPI-613® (Dose level -1.0 250 mg/m^2)	CPI-613® is a mitochondrial metabolism inhibitor. CPI-613® is a lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells.
DRUG	CPI-613® (Dose level 1.0 500 mg/m^2)	CPI-613® is a mitochondrial metabolism inhibitor. CPI-613® is a lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells.
DRUG	CPI-613® (Dose level 2.0 1,000 mg/m^2)	CPI-613® is a mitochondrial metabolism inhibitor. CPI-613® is a lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells.
DRUG	CPI-613® (Dose level 3.0 1,500 mg/m^2)	CPI-613® is a mitochondrial metabolism inhibitor. CPI-613® is a lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells.
DRUG	CPI-613® Maximum Tolerated Dose (MTD)	MTD will be determined by testing increasing doses of CPI-613®, starting from 500 mg/m\^2 and up to 1,500 mg/m\^2, on dose escalation cohorts of three patients (maximum 24 patients) in combination with Gem-RT therapy. MTD reflects the highest drug dose that does not cause unacceptable adverse effects, with a target dose-limiting toxicity (DLT) rate of 30%. Final dose will be revised as appropriate.
DRUG	Gemcitabine	Subjects will be administered 400 mg/m\^2 gemcitabine once per week by IV infusion over approximately 30 minutes for six weeks.
RADIATION	Intensity-modulated Radiation Therapy	1.8 Gy per fraction, 5 fractions per week, 30 fractions total (54 Gy) across six weeks.

Timeline

• Start date: 2022-10-31
• Primary completion: 2025-07-08
• Completion: 2025-07-08
• First posted: 2022-04-13
• Last updated: 2025-11-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study