CPI-613 in Combination With Modified FOLFIRINOX in Patients With Locally Advanced Pancreatic Cancer

A Phase II Open-Label Clinical Trial of CPI-613 in Combination With Modified FOLFIRINOX in Patients With Locally Advanced Pancreatic Cancer and Good Performance Status

This study is a single arm, phase II trial, of 45 patients with locally advanced pancreatic ductal adenocarcinoma. The efficacy of the novel drug and mitochondrial inhibitor, CPI-613, in conjunction with standard-of-care FOLFRINOX, as a first-line therapy will be evaluated. Pre-treatment, diagnostic biopsy tissue will be collected when available, and clinical data will be evaluated to determine if the combination results in improved overall survival compared to historical experience.

Primary Objective:

1) To determine if CPI-613 increases overall survival (OS) when used in combination with mFOLFIRINOX, in patients with locally advanced pancreatic cancer.

Secondary (Exploratory) Objectives:

1. To assess the safety of CPI-613 + mFOLFIRINOX combination in patients with locally advanced pancreatic cancer.
2. To collect tissue specimens for future correlative studies
3. To estimate median progression free survival (PFS) when CPI- 613 is used in combination with mFOLFIRINOX, in patients with locally advanced pancreatic cancer.
4. To estimate the percent resected when CPI-613 is used in combination with mFOLFIRINOX in patients with locally advanced pancreatic cancer

Inclusion Criteria:

• Cytologically confirmed pancreatic adenocarcinoma

• Locally advanced (including unresectable or borderline resectable) pancreatic cancer based on CT imaging, as determined by the PI

• Eastern Cooperative Oncology Group (ECOG) performance status being 0-1 within 1 week of planned start of therapy.

• Expected survival >3 months.

• Male and female patients 18 to not older than 80 years of age

• 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 during the study, unless documentation of infertility exists.

• Laboratory values ≤2 weeks must be:

  • Adequate hematologic (granulocyte count ≥1500/mm3; white blood cell [WBC] ≥3500 cells/mm3; platelet count ≥100,000 cells/mm3; absolute neutrophil count [ANC] ≥1500 cells/mm3; and hemoglobin ≥9 g/dL).
  • Adequate hepatic function (aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL], alanine aminotransferase [ALT/SGPT] ≤3x UNL, bilirubin ≤1.5x UNL).
  • Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 μmol/L).
  • Adequate coagulation ("International Normalized Ratio" or INR must be <1.5) unless on therapeutic blood thinners.

• No evidence of clinically significant active infection and no serious infection within the past month.

• Mentally competent, ability to understand and willingness to sign the informed consent form.

Exclusion Criteria:

• Patients under the age of 18 or older than 80 years of age
• Endocrine or acinar pancreatic carcinoma
• Resectable pancreatic cancer
• Metastatic pancreatic cancer based on imaging
• Prior surgical or medical treatment for pancreatic cancer
• Patients 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.
• Serious medical illness that would potentially increase patients' risk for toxicity
• Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease).
• Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown).
• Lactating females.
• Fertile men unwilling to practice contraceptive methods during the study period.
• Life expectancy less than 3 months.
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
• Unwilling or unable to follow protocol requirements.
• Active including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction.
• Patients with a history of myocardial infarction that is <3 months prior to registration.
• Evidence of active infection, or serious infection within the past month.
• Patients with known HIV infection.
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient.