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

• Status: Completed
• Trial end date: 2018-02-28
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nathan Bahary, MD; University of Pittsburgh
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Hydroxychloroquine; Paclitaxel

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.