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 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 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 of the study and must
have a negative serum or urine pregnancy test within 1 week prior to treatment
initiation, at the end of systemic exposure and between the cycles if the menstrual
period is delayed by over 30 days.

- Adult subjects of child bearing potential must agree to use double barrier
contraceptive measure, 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] Alanine
aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present)
Bilirubin ≤1.5x UNL); does not apply to subjects with Gilbert's syndrome
Serum albumin > 3.0 g/dL

- Adequate renal function:

- Serum creatinine clearance CLcr > 30 mL/min)

- Adequate coagulation function:

- International Normalized Ratio or INR must be <1.5 unless on therapeutic
blood thinners)

- No evidence of active infection and no serious infection within the past 30 days.

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

EXCLUSION CRITERIA

- Endocrine or acinar pancreatic carcinoma

- Known cerebral metastases, central nervous system (CNS), or epidural tumor

- Prior treatment with any chemotherapy for metastatic adenocarcinoma of the pancreas

- Completion of a gemcitabine-based adjuvant chemotherapy regimen within less than 6
months at the time of screening.

- Receipt of neoadjuvant or adjuvant FOLFIRINOX therapy

- Presence of clinically significant abdominal ascites

- 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 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)

- NAP

- 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 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

- Patients with a history of myocardial infarction that is <3 months prior to
registration

- Evidence of active infection, or serious infection within the past 30 days.

- Patients with known HIV infection

- Patients who have received cancer immunotherapy of any type within the past 2 weeks
prior to initiation of CPI-613 treatment (steroids given for supportive care or in
response to allergic reactions are allowed at any time)

- Requirement for immediate palliative treatment of any kind including surgery

- No 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

- Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or
inhibitors during treatment with irinotecan

- 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)

- 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