randomized phase ii trial of pre-operative gemcitabine and nab paclitacel with or with out hydroxychloroquine

Conditions: Pancreatic Cancer

Summary: this is a randomized phase ii trial that will examine the ability of the hydroxychloroquine to improve the clinical activity of a pre-operative regimen of gemcitabine and nab-paclitaxel in subjects with potentially resectable adenocarcinoma of the pancreas. eligible subjects will receive 2 cycles of gemcitabine and nab-paclitaxel (day 1, 8, 15) with or without hydrocychloroquine followed by surgical resection. primary endpoint will be histologic response as graded by evans criteria. secondary endpoints will be ca19-9 response and pet response. pre and post treatment tissue biopsies will be obtained to assess for levels of autophagy in tumor, liver and peripheral blood.


Eligibility criteria:
inclusion criteria: * subjects with biopsy-proven potentially resectable or borderline adenocarcinoma of the pancreas as determined by national comprehensive cancer network (nccn) criteria * karnofsky performance status of 70-100% * no active second malignancy except for basal cell carcinoma of the skin * patient has adequate biological parameters as demonstrated by the following blood counts at screening * absolute neutrophil count (anc) ≥1.5 × 109/l; * platelet count ≥100,000/mm3 (100 × 109/l); * hemoglobin (hgb) ≥9 g/dl. * patient has the following blood chemistry levels at baseline * aspartate aminotransferase (ast) (sgot), alanine transaminase (sgpt) ≤2.5 × upper limit of normal range (uln) * total bilirubin ≤uln * serum creatinine ≤ 1.5mg/dl or calculated creatinine clearance ≥ 50 for those patients with creatinine greater than 1.5 * prothrombin time (pt)within normal limits (wnl). if patient is on warfarin for prophylactic clot presentation for indwelling catheter, partial pt/ptt may be +/- 15 % * thromboplastin time (ptt) wnl. if patient on warfarin for prophylactic clot presentation for indwelling catheter, pt/ptt may be +/- 15 % * age \>18 years. * patient must be able to swallow enteral medications with no requirement for a feeding tube. patient's must not have intractable nausea or vomiting which prohibits the patient from oral medications * 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 randomization. * prior use of radiotherapy or investigational agents for pancreatic cancer. * any evidence of metastasis to distant organs (liver, lung, peritoneum). * symptomatic evidence of gastric outlet obstruction * inability to adhere to study and/or follow-up procedures * history of allergic reactions or hypersensitivity to the study drugs (hydroxychloroquine, gemcitabine, abraxane). * 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 randomization to rule out pregnancy. * 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 electrocardiogram (ekg) with corrected qt interval (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. * patient with a history of interstitial lung disease, history of slowly progressive dyspnea, sarcoidosis, silicosis, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis * patient with known active infection with hiv, hepatitis b or hepatitis c * patients requiring use of warfarin for therapeutic purposes.

Keywords: pancreatic cancer, resectable adenocarcinoma of the pancreas