Neoadjuvant mFOLFIRINOX With Perioperative Oral Hydroxychloroquine in Resectable Pancreatic Adenocarcinoma

Inclusion Criteria * Subjects with biopsy-proven adenocarcinoma of the pancreas * Pancreatic protocol helical CT scan demonstrating absence of venous or arterial involvement, consistent with NCCN guidelines for resectable disease * ECOG performance status ≤ 1 * No active second malignancy except for basal cell carcinoma of the skin * Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by: * Serum creatinine level ≤1.5 the upper limits of normal * Serum total bilirubin level ≤1.5 X ULN * White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100x109 per ml * For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria * Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection. * Subjects who have received chemotherapy within 12 months prior to study entry. * Subjects who are found to have loss-of-function mutations in DPYD or UGTA1 by Oneome pharmacogenomic testing, resulting in increased risk of mFOLFIRINOX toxicity. DPYD mutations have been noted in 5% of the overall population. Homozygous UGT1A1 mutations have been noted in 10% of North Americans. * Prior use of radiotherapy or investigational agents for pancreatic cancer. * Any evidence of metastasis to distant organs (liver, lung, peritoneum). * Cross sectional imaging suggesting portal vein, superior mesenteric artery, hepatic artery involvement that would make the patient borderline resectable or locally advanced * Symptomatic or endoscopic evidence of gastric outlet obstruction. * Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin. * Inability to adhere to study and/or follow-up procedures. * History of allergic reactions or hypersensitivity to the study drugs (chloroquine, hydroxychloroquine, 5-Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan). * Other concurrent experimental therapy. * The effects of HCQ, and mFOLFIRINOX on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All females of childbearing potential must have a blood test or urine study within two weeks prior to registration to rule out pregnancy. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well. * Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HCQ and mFOLFIRINOX is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future. * Due to the risk of disease exacerbation, patients with porphyria are ineligible. * Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist who agrees to monitor the patient for exacerbations. * Patients requiring the use of enzyme-inducing anti-epileptic medication that includes: phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are excluded. * Patients with previously documented macular degeneration or diabetic retinopathy are excluded. * Baseline EKG with QTc \>470 msec (including subjects on medication). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.