Ivosidenib and Combination Chemotherapy (mFOLFIRINOX) for the Treatment of Resectable Pancreatic Cancer

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma or adenosquamous carcinoma.
• Subjects must have resectable right-sided (head/neck/uncinate) pancreatic cancer based on computed tomography (CT) or magnetic resonance imaging (MRI) imaging (pancreas protocol CT of the abdomen and pelvis if possible, MRI with contrast or CT with intravenous (IV) contrast in the absence of a pancreas protocol CT scan, CT of the chest with or without contrast) as determined by the principal investigator (PI) or Co-investigators. Patients with contrast allergies may be permitted without contrast scans if approved by the PI or Co-Investigators for safety reasons.
• Male or female subjects age >= 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status being 0-1 within 2 weeks of planned start of therapy.
• White blood cell (WBC) >= 3500 cells/mm^3 (within 2 weeks of cycle 1 day 1 [C1D1]).
• Platelet count >= 100,000 cells/mm^3 (within 2 weeks of C1D1).
• Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 2 weeks of C1D1).
• Hemoglobin >= 8 g/dL (within 2 weeks of C1D1).
• Aspartate aminotransferase (ALT)/(serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT)/(serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (within 2 weeks of C1D1).
• Bilirubin < 3 x UNL (within 2 weeks of C1D1).
• Serum creatinine =< 2.0 mg/dL or 177 umol/L (within 2 weeks of C1D1).
• “International Normalized Ratio” or INR must be =< 1.5) unless on therapeutic blood thinners (within 2 weeks of C1D1).
• Screening hemoglobin (Hgb) A1C < 7.0%
• 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 or chronic infection requiring ongoing antibiotics during the study period.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Subjects under the age of 18 years of age.
• Subjects with unresectable pancreatic cancer or resectable left-sided (body/tail) pancreatic cancer.
• Subjects with endocrine or acinar pancreatic carcinoma.
• Subjects with locally advanced or recurrent pancreatic cancer.
• Subjects with metastatic pancreatic cancer based on imaging.
• Subjects who have received prior radiation therapy, surgical or medical treatment for pancreatic cancer.
• Subjects receiving any other standard or investigational treatment for their pancreatic ductal adenocarcinoma (PDA).
• 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 ivosidenib is unknown. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with ivosidenib, breastfeeding should be discontinued if the mother is treated with ivosidenib. These potential risks may also apply to other agents used in this study.
• Fertile men unwilling to practice contraceptive methods during the study period.
• Subjects with a life expectancy less than 3 months.
• Subjects with a serious medical illness that would potentially increase subjects’ risk for toxicity.
• Subjects with any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease).
• Subjects with a history of myocardial infarction that is < 3 months prior to registration.
• Subjects 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 requiring medications that interact with ivosidenib, symptomatic myocardial infarction or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects who are known to be human immunodeficiency virus (HIV)-positive and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ivosidenib.