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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Pancreatic Cancer
Intervention	Drug: gemcitabine Drug: abraxane Drug: hydroxychloroquine
Phase	Phase 2
Sponsor	University of Pittsburgh
Responsible Party	University of Pittsburgh
ClinicalTrials.gov Identifier	NCT01978184
First Received	October 30, 2013
Last Updated	November 6, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	October 30, 2013
Last Updated Date	November 6, 2013
Start Date	November 2013
Estimated Primary Completion Date	November 2017
Current Primary Outcome Measures	Histologic response to pre-operative gemcitabine/ nab-paclitaxel [Time Frame: up to 3 years] [Designated as safety issue: No]
Current Secondary Outcome Measures	Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel [Time Frame: Up to 3 years] [Designated as safety issue: No] Rate of R0 resection and positive lymph node ratio [Time Frame: Up to 3 years] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Official Title	Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Brief 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.
Detailed Description	Not Provided
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
Condition	Pancreatic Cancer
Intervention	Drug: gemcitabine Other Names: GemzarDrug: abraxane Other Names: nab-PaclitacelDrug: hydroxychloroquine Other Names: Plaquenil
Study Arm (s)	Experimental: gemcitabine and abraxane Gemcitabine and Abraxane will be administered on an outpatient basis on Days 3, 10, 17, 31, 38, and 45 as an intravenous infusion. The dose on Day 3 will be 1000 mg/m of gemcitabine followed by a 125 mg/m2 of abraxane and the infusion will take 1 hour. The second dose and infusion time may be decreased. Prior to each gemcitabine infusion, subjects will be pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician. Experimental: gemcitabine, abraxane and hydroxychloroquine Gemcitabine and Abraxane will be administered on an outpatient basis on Days 3, 10, 17, 31, 38, and 45 as an intravenous infusion. The dose on Day 3 will be 1000 mg/m of gemcitabine followed by a 125 mg/m2 of abraxane and the infusion will take 1 hour. The second dose and infusion time may be decreased. Prior to each gemcitabine infusion, subjects will be pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician. Hydroxychloroquine is an oral drug (capsule) that subjects will take once or twice a day at home. The dose of hydroxychlorquien will be 1200mg. This is an experimental drug. Subjects will take their first dose of hydroxychloroquine on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and will continue to take it every day until the day before surgery.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	60
Estimated Completion Date	November 2017
Estimated Primary Completion Date	November 2017
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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01978184
Other Study ID Numbers	UPCI# 13-074
Has Data Monitoring Committee	Yes
Information Provided By	University of Pittsburgh
Study Sponsor	University of Pittsburgh
Collaborators	Not Provided
Investigators	Principal Investigator: Herbert Zeh, MD University of Pittsburgh CancerCenters
Verification Date	November 2013

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