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

Inclusion Criteria

• Histologically or cytologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
• No prior treatments for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is allowed provided completed > 6 months prior to disease recurrence)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Male and female patients 18 - 75 years of age
• Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1)
• Expected survival >3 months
• 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
• 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
• At least 2 weeks must have elapsed from any prior surgery with resolution of any sequela for randomization
• 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 480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula (i.e. QTcF)
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of long QT syndrome)
• The use of concomitant medications that prolong the QT/QTc intervals
• 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 a