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

Inclusion Criteria:

* Participants must have histologically or cytologically confirmed pancreatic adenocarcinoma.
* Participants must have locally advanced (including unresectable or borderline resectable) pancreatic cancer based on CT or 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 PI or Co-investigators. Participants 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 01 within 1 week of planned start of therapy.
* Participants must have normal organ and marrow function as defined below \< 2 weeks must be:

  * Adequate hematologic (white blood cell \[WBC\] \>= 3500 cells/mm3; platelet count \>= 100,000 cells/mm3; absolute neutrophil count \[ANC\] \>=1500 cells/mm3; and hemoglobin \>=8 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.
* 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.
* Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Participants with endocrine or acinar pancreatic carcinoma.
* Participants with resectable pancreatic cancer.
* Participants with metastatic pancreatic cancer based on imaging.
* Participants who have received prior surgical or medical treatment for pancreatic cancer.
* Participants 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.
* Participants with a life expectancy less than 3 months.
* Participants with a serious medical illness that would potentially increase participants' risk for toxicity
* Participants with any active uncontrolled bleeding, and any participnats with a bleeding diathesis (e.g., active peptic ulcer disease).
* Participants with a history of myocardial infarction that is \<3 months prior to registration.
* Participants 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.
* Participants who are known to be HIV-positive and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with CPI-613.