Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas

Inclusion Criteria: 1. Histologically or cytologically confirmed metastatic Stage IV adenocarcinoma of the pancreas 2. No prior treatments for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is allowed provided completed \> 6 months prior to disease recurrence) 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 4. Male and female patients 18 - 75 years of age 5. Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) 6. Expected survival \>3 months 7. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted highly effective contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive(s), intrauterine hormone releasing system (IUS), bilateral tubal occlusion or vasectomized partner) during and for 6 months after last study dose and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation, at monthly interval (day 1 of every even numbered cycle), at the end of systemic exposure, and at 30 days after the systemic exposure 8. Males with female partners (of childbearing potential) and female partners (of child bearing potential) with male partners must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to oral contraception or avoidance of intercourse during the study and for 6 months after last study dose is received 9. At least 2 weeks must have elapsed from any prior surgery with resolution of any sequela for randomization 10. Laboratory values ≤2 weeks prior to randomization must be: * Adequate hematologic values * Platelet count ≥100,000 cells/mm3 or ≥100 bil/L; * Absolute neutrophil count \[ANC\] ≥1,500 cells/mm3 or ≥1.5 bil/L; * Hemoglobin ≥9 g/dL or ≥90 g/L) * Adequate hepatic function * Aspartate aminotransferase \[AST/SGOT\] ≤3x upper normal limit \[UNL\] (≤5x UNL if liver metastases present) * Alanine aminotransferase \[ALT/SGPT\] ≤3x UNL (≤5x UNL if liver metastases present) * Bilirubin (≤1.5x UNL); bilirubin ≤ 2.5 x ULN for subjects with Gilbert's syndrome * Serum albumin \> 3.0 g/dL * Adequate renal function serum creatinine clearance CLcr \> 30 mL/min). (Cocroft-Gault Formula should be used for CrCl calculation) * Adequate coagulation function • International Normalized Ratio or INR must be \<1.5 unless on therapeutic blood thinners) 11. No evidence of active infection and no serious infection within the past 30 days. 12. Mentally competent, ability to understand and willingness to sign the informed consent form. Exclusion Criteria: 1. Endocrine or acinar pancreatic carcinoma 2. Known cerebral metastases, central nervous system (CNS), or epidural tumor 3. Prior treatment with any chemotherapy for metastatic adenocarcinoma of the pancreas 4. Completion of a gemcitabine-based adjuvant chemotherapy regimen within less than 6 months at the time of screening. 5. Receipt of neoadjuvant or adjuvant FOLFIRINOX therapy if \<6 months prior to disease recurrence 6. Patients with hypersensitivity to devimistat, FFX treatment or any of their excipients 7. Presence of clinically significant abdominal ascites 8. Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of devimistat treatment 9. Serious medical illness that would potentially increase patients' risk for toxicity 10. Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease) 11. Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of study treatment 12. Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at screening 13. Female patients of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for 6 months after the last dose of study treatment 14. Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of study treatment 15. Male patients unwilling to abstain from donating sperm during treatment and for 6 months after completion of study treatment 16. Life expectancy less than 3 months 17. Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients 18. Unwilling or unable to follow protocol requirements 19. Active heart disease including but not limited to symptomatic congestive heart failure (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction 20. Patients with a history of myocardial infarction that is \<3 months prior to registration 21. Evidence of active infection, or serious infection within the past 30 days. 22. Patients with known HIV infection 23. Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of devimistat treatment (steroids given for supportive care or in response to allergic reactions are allowed at any time) 24. Requirement for immediate palliative surgery, radiation or chemotherapy of any kind. Stenting for bile duct obstruction and need for pain medications are allowed provided all other inclusion criteria are met 25. Prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated cancer from which the patient has been disease-free for at least 3 years prior to screening 26. Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or inhibitors during treatment with irinotecan 27. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula (i.e. QTcF) 28. A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of long QT syndrome) 29. The use of concomitant medications that prolong the QT/QTc intervals 30. Contraindications to any of the FFX treatment as follows: Folinic Acid * Calcium Folinate is contraindicated in patients who have previously shown hypersensitivity to folinate or any of the excipients. * Calcium Folinate Injection is contraindicated in the treatment of pernicious anemia or other megaloblastic anemias where vitamin B12 is deficient. Its use can lead to an apparent response of the hematopoietic system, but neurological damage may occur or progress if already present. * Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets. Fluorouracil/5FU * Fluorouracil is contraindicated in patients who have any known hypersensitivity to fluorouracil, are seriously debilitated or are suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents, or who are suffering from a potentially serious infection. * Fluorouracil is strictly contraindicated in pregnant or breast-feeding women. * Flourouracil should not be used in the management of non-malignant disease. * Fluorouracil must not be taken or used concomitantly with brivudin, sorivudine and analogues. Brivudin, sorivudine and analogues are potent inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD) which degrades fluorouracil * In patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity Oxaliplatin * Oxaliplatin is contraindicated in patients who have a known history of hypersensitivity to oxaliplatin or to any of the excipients * are breast-feeding. * have myelosuppression prior to starting first course, as evidenced by baseline neutrophils \<2x109/l and/or platelet count of \<100x109l. * have a peripheral sensitive neuropathy with functional impairment prior to first course. * have a severely impaired renal function (creatinine clearance less than 30 ml /min) Irinotecan * Chronic inflammatory bowel disease and/or bowel obstruction * History of severe hypersensitivity reactions to Irinotecan hydrochloride trihydrate or to any of the excipients * Bilirubin \> 3 times the ULN * Severe bone marrow failure. * WHO performance status \> 2. * Concomitant use with St John's wort