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

Primary Objective:

1) To determine if CPI-613 increases overall survival (OS) when used in combination with
mFOLFIRINOX, in patients with locally advanced pancreatic cancer.

Secondary (Exploratory) Objectives:

1. To assess the safety of CPI-613 + mFOLFIRINOX combination in patients with locally
advanced pancreatic cancer.

2. To collect tissue specimens for future correlative studies

3. To estimate median progression free survival (PFS) when CPI- 613 is used in combination
with mFOLFIRINOX, in patients with locally advanced pancreatic cancer.

4. To estimate the percent resected when CPI-613 is used in combination with mFOLFIRINOX in
patients with locally advanced pancreatic cancer

Inclusion Criteria:

- Cytologically confirmed pancreatic adenocarcinoma

- Locally advanced (including unresectable or borderline resectable) pancreatic cancer
based on CT imaging, as determined by the PI

- Eastern Cooperative Oncology Group (ECOG) performance status being 0-1 within 1 week
of planned start of therapy.

- Expected survival >3 months.

- Male and female patients 18 to not older than 80 years of age

- 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 during the study, unless
documentation of infertility exists.

- Laboratory values ≤2 weeks must be:

- Adequate hematologic (granulocyte count ≥1500/mm3; white blood cell [WBC] ≥3500
cells/mm3; platelet count ≥100,000 cells/mm3; absolute neutrophil count [ANC]
≥1500 cells/mm3; and hemoglobin ≥9 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.

- No evidence of clinically significant active infection and no serious infection within
the past month.

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

Exclusion Criteria:

- Patients under the age of 18 or older than 80 years of age

- Endocrine or acinar pancreatic carcinoma

- Resectable pancreatic cancer

- Metastatic pancreatic cancer based on imaging

- Prior surgical or medical treatment for pancreatic cancer

- Patients 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.

- 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).

- Pregnant women, or women of child-bearing potential not using reliable means of
contraception (because the teratogenic potential of CPI-613 is unknown).

- 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 including but not limited to symptomatic congestive heart failure, 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 month.

- Patients with known HIV infection.

- Any condition or abnormality which may, in the opinion of the investigator, compromise
the safety of the patient.