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

NCT05325281 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO00043904
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Pancreas Adenocarcinoma

Keywords

CPI-613; Devimistat; intensity-modulated radiation therapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of CPI-613®

  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.

  Initiation of treatment to 30 days after treatment

Secondary Outcomes (1)

• The number of subjects with adverse events related to the treatment

  Start of study treatment until 30 days after completion of study treatment.

Study Arms (5)

CPI-613® (Dose level -1.0 250 mg/m^2)

EXPERIMENTAL

Dose escalation/de-escalation for CPI-613® (devimistat) will be conducted using a Bayesian optimal interval (BOIN) design. Gemcitabine will be infused over 30 minutes at a fixed dose of 400 mg/m\^2 weekly. Intensity-modulated radiation therapy will be administered at 54 Gy in 30 fractions of 1.8 Gy per fraction, with five fractions given per week. CPI-613® will be given once per week by IV infusion.

Drug: CPI-613® (Dose level -1.0 250 mg/m^2); Drug: Gemcitabine; Radiation: Intensity-modulated Radiation Therapy

CPI-613® (Dose level 1.0 500 mg/m^2)

EXPERIMENTAL

Dose escalation/de-escalation for CPI-613® (devimistat) will be conducted using a Bayesian optimal interval (BOIN) design. Gemcitabine will be infused over 30 minutes at a fixed dose of 400 mg/m\^2 weekly. Intensity-modulated radiation therapy will be administered at 54 Gy in 30 fractions of 1.8 Gy per fraction, with five fractions given per week. CPI-613® will be given once per week by IV infusion.

Drug: CPI-613® (Dose level 1.0 500 mg/m^2); Drug: Gemcitabine; Radiation: Intensity-modulated Radiation Therapy

CPI-613® (Dose level 2.0 1,000 mg/m^2)

EXPERIMENTAL

Dose escalation/de-escalation for CPI-613® (devimistat) will be conducted using a Bayesian optimal interval (BOIN) design. Gemcitabine will be infused over 30 minutes at a fixed dose of 400 mg/m\^2 weekly. Intensity-modulated radiation therapy will be administered at 54 Gy in 30 fractions of 1.8 Gy per fraction, with five fractions given per week. CPI-613® will be given once per week by IV infusion.

Drug: CPI-613® (Dose level 2.0 1,000 mg/m^2); Drug: Gemcitabine; Radiation: Intensity-modulated Radiation Therapy

CPI-613® (Dose level 3.0 1,500 mg/m^2)

EXPERIMENTAL

Dose escalation/de-escalation for CPI-613® (devimistat) will be conducted using a Bayesian optimal interval (BOIN) design. Gemcitabine will be infused over 30 minutes at a fixed dose of 400 mg/m\^2 weekly. Intensity-modulated radiation therapy will be administered at 54 Gy in 30 fractions of 1.8 Gy per fraction, with five fractions given per week. CPI-613® will be given once per week by IV infusion.

Drug: CPI-613® (Dose level 3.0 1,500 mg/m^2); Drug: Gemcitabine; Radiation: Intensity-modulated Radiation Therapy

CPI-613® Maximum Tolerated Dose (MTD)

EXPERIMENTAL

MTD of CPI-613® from initiation of treatment to 30 days after treatment. 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: CPI-613® (Dose level -1.0 250 mg/m^2); Drug: CPI-613® (Dose level 1.0 500 mg/m^2); Drug: CPI-613® (Dose level 2.0 1,000 mg/m^2); Drug: CPI-613® (Dose level 3.0 1,500 mg/m^2); Drug: CPI-613® Maximum Tolerated Dose (MTD); Drug: Gemcitabine; Radiation: Intensity-modulated Radiation Therapy

Interventions

CPI-613® (Dose level -1.0 250 mg/m^2) DRUG

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.

Also known as: Devimistat, alpha-lipoic acid analogue CPI-613

CPI-613® (Dose level -1.0 250 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

CPI-613® (Dose level 1.0 500 mg/m^2) DRUG

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.

Also known as: Devimistat, alpha-lipoic acid analogue CPI-613

CPI-613® (Dose level 1.0 500 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

CPI-613® (Dose level 2.0 1,000 mg/m^2) DRUG

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.

Also known as: Devimistat, alpha-lipoic acid analogue CPI-613

CPI-613® (Dose level 2.0 1,000 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

CPI-613® (Dose level 3.0 1,500 mg/m^2) DRUG

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.

Also known as: Devimistat, alpha-lipoic acid analogue CPI-613

CPI-613® (Dose level 3.0 1,500 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

CPI-613® Maximum Tolerated Dose (MTD) DRUG

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.

Also known as: Devimistat, alpha-lipoic acid analogue CPI-613

CPI-613® Maximum Tolerated Dose (MTD)

Gemcitabine DRUG

Subjects will be administered 400 mg/m\^2 gemcitabine once per week by IV infusion over approximately 30 minutes for six weeks.

Also known as: Gemzar®

CPI-613® (Dose level -1.0 250 mg/m^2); CPI-613® (Dose level 1.0 500 mg/m^2); CPI-613® (Dose level 2.0 1,000 mg/m^2); CPI-613® (Dose level 3.0 1,500 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

Intensity-modulated Radiation Therapy RADIATION

1.8 Gy per fraction, 5 fractions per week, 30 fractions total (54 Gy) across six weeks.

CPI-613® (Dose level -1.0 250 mg/m^2); CPI-613® (Dose level 1.0 500 mg/m^2); CPI-613® (Dose level 2.0 1,000 mg/m^2); CPI-613® (Dose level 3.0 1,500 mg/m^2); CPI-613® Maximum Tolerated Dose (MTD)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Pathologically confirmed (histologic or cytologic) adenocarcinoma of the pancreas.
• Patients should have an inoperable disease (locally advanced, oligometastatic, or medically inoperable) and, based on the review of the institutional pancreatic tumor board, should otherwise benefit from chemoradiation for definitive local control of the primary tumor.
• Patients with and without regional adenopathy are eligible.
• History/physical examination, including a collection of weight and vital signs, within 30 days prior to treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 14 days of study entry.
• Imaging requirements are to include
• Diagnostic abdominal/pelvic CT with IV contrast or abdominopelvic magnetic resonance (MR) scan with perfusion and diffusion-weighted sequences within 45 days prior to study entry.
• Chest CT scan or X-ray within 45 days prior to study entry.
• Radiation treatment planning abdominal CT. A recommended abdominal MR will be done as a simulation (SIM) scan with interpretation. The CT SIM will not be done with interpretation. Positron emission tomography (PET) scan and MRI are both optional but encouraged. Abdominal MR scans for staging and radiation planning and follow-up are optional but encouraged.
• Heme Onc (Chem 24) and cancer antigen 19-9/ carcinoembryonic antigen (CEA) within 30 days prior to treatment, as follows:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3.
• Platelets ≥ 100,000 cells/mm3.
• Hemoglobin ≥ 8.0g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dl is acceptable).
• Not on hemodialysis.

You may not qualify if:

• Prior invasive malignancy (except nonmelanomatous skin cancer, noninvasive breast cancer \[ductal carcinoma in situ\], or prostate cancer under active surveillance). Other malignancies are allowed if the patient has been disease free for a minimum of two years.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Any major surgery within 28 days prior to study entry, except colonic stent placement, intestinal diversion without resection, exploratory laparotomy and laparoscopy or vascular access insertion.
• Life expectancy less than two months.
• Severe, active co-morbidity, defined as follows:
• Any unresolved bowel or bile duct obstruction, or
• Symptomatic myocardial ischemia, or
• uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics is excluded and first-degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB) / right bundle branch block (RBBB) will not be excluded), or
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
• Any active uncontrolled bleeding or patients with a bleeding diathesis.
• Serious psychiatric illness (e.g., depression, psychosis) or medical conditions that in the opinion of investigator could interfere with treatment.
• Concurrent therapy with approved or investigational anticancer therapeutics other that what is stipulated by the protocol.
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or HBsAg (HBV surface antigen).
• Known to be HIV seropositive and on anti-HIV drugs because of the unknown interactions between these drugs and the study agents.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Cornerstone Pharmaceuticals: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Khan HY, Kamgar M, Aboukameel A, Bannoura S, Chung BY, Li Y, Hallak MNA, Philip PA, Tsai S, Luther S, Hall WA, Azmi AS. Targeting Cellular Metabolism With CPI-613 Sensitizes Pancreatic Cancer Cells to Radiation Therapy. Adv Radiat Oncol. 2022 Nov 9;8(1):101122. doi: 10.1016/j.adro.2022.101122. eCollection 2023 Jan-Feb.

  PMID: 36479231 DERIVED

MeSH Terms

Interventions

devimistat; Gemcitabine; Radiotherapy, Intensity-Modulated

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Mandana Kamgar, MD, MPH

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 13, 2022
• Study Start: October 31, 2022
• Primary Completion: July 8, 2025
• Study Completion: July 8, 2025
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)