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

NCT ID: NCT01978184

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2018-02-28

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

gemcitabine

Intervention Type: DRUG

abraxane

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

gemcitabine

Intervention Type: DRUG

abraxane

Intervention Type: DRUG

hydroxychloroquine

Intervention Type: DRUG

Interventions

gemcitabine

Intervention Type: DRUG

abraxane

Intervention Type: DRUG

hydroxychloroquine

Intervention Type: DRUG

Other Intervention Names

Gemzar; nab-Paclitacel; Plaquenil

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nathan Bahary, MD

OTHER

Sponsor Role: lead

Responsible Party

Nathan Bahary, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Herbert Zeh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh CancerCenters

Locations

Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Miller-Ocuin JL, Liang X, Boone BA, Doerfler WR, Singhi AD, Tang D, Kang R, Lotze MT, Zeh HJ 3rd. DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth. Oncoimmunology. 2019 Jun 11;8(9):e1605822. doi: 10.1080/2162402X.2019.1605822. eCollection 2019.

Reference Type: DERIVED

PMID: 31428515 (View on PubMed)

Boone BA, Murthy P, Miller-Ocuin J, Doerfler WR, Ellis JT, Liang X, Ross MA, Wallace CT, Sperry JL, Lotze MT, Neal MD, Zeh HJ 3rd. Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer. 2018 Jun 22;18(1):678. doi: 10.1186/s12885-018-4584-2.

Reference Type: DERIVED

PMID: 29929491 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UPCI# 13-074

Identifier Type: -

Identifier Source: org_study_id