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CPI-613 and Combination Chemotherapy in Treating Patients with Locally Advanced Pancreatic Cancer

Trial Status: Active

This phase II trial studies the best dose of CPI-613 and how well it works with combination chemotherapy in treating patients with pancreatic cancer that has spread to nearby tissues or lymph nodes (locally advanced). CPI-613 inhibits energy production in cells. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPI-613 and combination chemotherapy may work better in treating patients with pancreatic cancer.

Inclusion Criteria

  • Subjects must have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma
  • Subjects must have locally advanced (including unresectable or borderline resectable) pancreatic cancer based on computed tomography (CT) or magnetic resonance imaging (MRI) imaging (pancreas protocol CT of the abdomen and pelvis if possible, MRI with contrast or CT with IV contrast in the absence of a pancreas protocol CT scan, CT of the chest with or without contrast) as determined by the principal investigator (PI) or co-investigators. Patients with contrast allergies may be permitted without contrast scans if approved by the PI or co-Investigators for safety reasons
  • Eastern Cooperative Oncology Group (ECOG) performance status being 0-1 within 2 weeks of planned start of therapy
  • White blood cell (WBC) >= 3500 cells/mm^3 (=< 2 weeks prior)
  • Platelet count >= 100,000 cells/mm^3 (=< 2 weeks prior)
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (=< 2 weeks prior)
  • Hemoglobin >= 8 g/dL (=< 2 weeks prior)
  • Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL) (=< 2 weeks prior)
  • Alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 2 weeks prior)
  • Bilirubin =< 1.5 x UNL (=< 2 weeks prior)
  • Serum creatinine =< 2.0 mg/dL or 177 umol/L (=< 2 weeks prior)
  • “International normalized ratio” or INR must be =< 1.5 unless on therapeutic blood thinners (=< 2 weeks prior)
  • Expected survival >= 3 months in the view of the PI or investigators
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
  • Fertile men must practice effective contraceptive methods (i.e. surgical sterilization, or a condom used with a spermicide) during the study, unless documentation of infertility exists
  • No evidence of clinically significant active infection and no serious infection within the past month requiring hospitalization
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Subjects with endocrine or acinar pancreatic carcinoma
  • Subjects with resectable pancreatic cancer
  • Subjects with metastatic pancreatic cancer based on imaging
  • Subjects who have received prior radiation therapy, surgical or medical treatment for pancreatic cancer
  • Subjects receiving any other standard or investigational treatment for their cancer with a primary goal of improving survival within the past 2 weeks prior to initiation of CPI-613 treatment
  • Pregnant women or breast feeding women, or women of child-bearing potential not using reliable means of contraception are excluded from this study because the teratogenic or abortifacient effects of CPI-613 is unknown. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CPI-613, breastfeeding should be discontinued if the mother is treated with CPI-613. These potential risks may also apply to other agents used in this study
  • Fertile men unwilling to practice contraceptive methods during the study period
  • Subjects with a life expectancy less than 3 months
  • Subjects with a serious medical illness that would potentially increase subjects’ risk for toxicity
  • Subjects with any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
  • Subjects with a history of myocardial infarction that is < 3 months prior to registration
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure or coronary artery disease, unstable angina pectoris, cardiac arrhythmia, symptomatic myocardial infarction or psychiatric illness/social situations that would limit compliance with study requirements
  • Subjects who are known to be human immunodeficiency virus (HIV)-positive and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with CPI-613


Case Comprehensive Cancer Center
Status: ACTIVE
Contact: Jeffrey Max Hardacre
Phone: 216-844-7047


I. To determine if devimistat (CPI-613) increases overall survival (OS) when used in combination with modified (m) oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil (FOLFIRINOX), in patients with locally advanced pancreatic cancer. (Standard Dose Cohort)

II. To determine a new maximum-tolerated dose (MTD) of CPI-613 when given in combination with mFOLFIRINOX. (Dose Escalation Cohort)


I. To assess the safety of CPI-613 + mFOLFIRINOX combination in patients with locally advanced pancreatic cancer. (Standard Dose Cohort)

II. To collect tissue specimens for future correlative studies. (Standard Dose Cohort)

III. To estimate median progression free survival (PFS) when CPI-613 is used in combination with mFOLFIRINOX, in patients with locally advanced pancreatic cancer. (Standard Dose Cohort)

IV. To estimate the percent resected when CPI-613 is used in combination with mFOLFIRINOX in patients with locally advanced pancreatic cancer. (Standard Dose Cohort)

V. To investigate the safety of higher doses of CPI-613 with mFOLFIRINOX in a small cohort of patients and redefine the MTD. (Standard Dose Cohort)

VI. Measurements of progression free survival (PFS) defined as time from study enrollment to progression or death from any cause. (Dose Escalation Cohort)

VII. Time to progression (TTP) defined as time from enrollment to progression. (Dose Escalation Cohort)

VIII. Surgical resection rates. (Dose Escalation Cohort)

IX. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 response rates including complete response, partial response and stable disease (complete response [CR]+partial response [PR]+stable disease [SD]). (Dose Escalation Cohort)

X. Complete pathologic response rates (CRp). (Dose Escalation Cohort)

XI. Resection margins. (Dose Escalation Cohort)


I. The importance of genetic or other molecular abnormalities as predictive biomarkers. (Standard Dose Cohort)

II. Serum CPI-613 and metabolite levels as markers of toxicity or efficacy. (Standard Dose Cohort)

III. Examine molecular markers from tissue biopsies prior to treatment, or from surgical specimens obtained at resection. (Dose Escalation Cohort)

IV. Collect serum metabolites when feasible, if funding allows. (Dose Escalation Cohort)

OUTLINE: This is a phase I, dose-escalation study of CPI-613 followed by a phase II study.

Patients receive CPI-613 intravenously (IV) on days 1 and 3, oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 90 minutes on day 1, irinotecan hydrochloride IV over 90 minutes on day 1, and fluorouracil IV over 46 hours over days 1-3. Treatment repeats every 2 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of 12 cycles, patients may receive additional therapy per clinicians’ recommendation.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for 2 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Jeffrey Max Hardacre

  • Primary ID CASE2218
  • Secondary IDs NCI-2018-03552
  • ID NCT03699319