CPI-613 and Combination Chemotherapy in Treating Patients with Locally Advanced Pancreatic Cancer
- 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 oral and 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
- 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
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.
I. Measurements of progression free survival (PFS) defined as time from study enrollment to progression or death from any cause.
II. Time to progression (TTP) defined as time from enrollment to progression.
III. Surgical resection rates.
IV. 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]).
V. Complete pathologic response rates (CRp).
VI. Resection margins.
I. The importance of genetic or other molecular abnormalities as predictive biomarkers.
II. Serum CPI-613 and metabolite levels as markers of toxicity or efficacy.
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 then every 3 months for 3 years.
Trial Phase Phase II
Trial Type Treatment
Case Comprehensive Cancer Center
Jeffrey Max Hardacre
- Primary ID CASE2218
- Secondary IDs NCI-2018-03552
- Clinicaltrials.gov ID NCT03699319