Study of Pre-surgery Gemcitabine + Hydroxychloroquine (GcHc) in Stage IIb or III Adenocarcinoma of the Pancreas

Inclusion Criteria:

* Subjects with biopsy-proven adenocarcinoma of the pancreas
* staged by IIb or greater by by EUS, or tumor greater than 2.6 cm on EUS or pancreatic protocol helical CT scan demonstrating venous involvement
* Karnofsky performance status \>/= 70.
* 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
* Age \>18 years.
* 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.
* Prior use of radiotherapy or investigational agents for pancreatic cancer.
* Any evidence of metastasis to distant organs (liver, lung, peritoneum).
* 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 (hydroxychloroquine, gemcitabine).
* Other concurrent experimental therapy.
* The effects of HCQ, and gemcitabine 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 gemcitabine 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.