Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: gemcitabine; abraxane; hydroxychloroquine
Intervention MeSH terms: Hydroxychloroquine; Gemcitabine; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer, resectable adenocarcinoma of the pancreas

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.