Patient case: 50-year-old male with pancreatic cancer; genetic feature: BRCA2

Clinical trial: Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine

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: 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.

Relevance to patient case: not relevant