Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Conditions
Pancreatic Cancer
Conditions: official terms
Pancreatic Neoplasms
Conditions: Keywords
Pancreatic Cancer, resectable adenocarcinoma of the pancreas
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: gemcitabine Type: Drug
Name: abraxane Type: Drug
Name: hydroxychloroquine Type: Drug
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Location
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Status: Recruiting
Contact: Herbert Zeh, MD - 412-692-2852 - zehxhx@UPMC.EDU
Start Date
November 2013
Completion Date
November 2017
Sponsors
University of Pittsburgh
Source
University of Pittsburgh
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page