Overview

This trial is active, not recruiting.

Condition pancreatic cancer
Treatments hydroxychloroquine, gemcitabine
Phase phase 1/phase 2
Sponsor University of Pittsburgh
Collaborator National Institutes of Health (NIH)
Start date October 2010
End date March 2016
Trial size 40 participants
Trial identifier NCT01128296, PO1101944, UPCI 09-122

Summary

The primary goal of the research study is to determine whether treating pancreatic cancer patients with hydroxychloroquine in combination with gemcitabine before surgery is safe. The secondary goal is to determine if this new treatment regimen can effectively treat pancreatic cancer. This study will test the safety and efficacy of this combination in two parts, or phases.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Hydroxychloroquine orally twice daily in combination with gemcitabine for 31 days prior to surgical resection
hydroxychloroquine Plaquenil
Oral dosing daily starting at 48 hours before first dose of gemcitabine (starting on Day -2) and for a total of 31 days (ending on Day 29), prior to surgical resection. Capsules are available in 200 mg strengths. Daily doses are 200, 400, 600, 800, 1000, or 1200 mg, and will be administered BID for doses above 200 mg.
gemcitabine Gemzar
Intravenous administration on Days 1 and 15, with the infusion given at the fixed dose rate of 10mg/m2/min (e.g. 150 min for a 1500 mg/m2 dose).

Primary Outcomes

Measure
To establish the safety and tolerability of a novel regimen of pre-operative oral hydroxychloroquine in combination with gemcitabine (GCHC) in patients with high risk stage IIb or III adenocarcinoma of the pancreas
time frame: During 31 days of study drug regimen

Secondary Outcomes

Measure
To establish the potential biologic activity and suitability for phase II study of GCHC, as determined by the rate of grade III or better histopathologic response.
time frame: Surgical resection after 31 days of study drug regimen
To establish the potential biological activity and suitability for phase II study of GCHC by radiographic tumor response, as assessed by [18F]- FDG PET.
time frame: Prior to and after 31 days of study drug regimen (pre-surgical resection)
Determine the effects of hydroxychloroquine on the plasma pharmacokinetics and metabolism of gemcitabine
time frame: Days 1, 2, 3, 16, and 17
Biomarker response (Ca 19-9), antibodies to cardiolipin, sMICA levels
time frame: Prior to and after 31 days of study drug regimen (pre-surgical resection), post-surgical resection, every 3 months until disease progression
Correlate the level of autophagy in resected pancreatic adenocarcinomas with measures of clinical outcome, histopathologic response and [18F]- FDG PET.
time frame: Surgical resection after 31 days of study drug regimen
Correlate the levels of autophagic markers in peripheral blood mononuclear cells with histopathologic response and changes in the [18F]- FDG PET activity.
time frame: Prior to and after 31 days of study drug regimen (pre-surgical resection), post-surgical resection, every 3 months until disease progression
Assess coagulation parameters during the protocol treatment.
time frame: Prior to and after 31 days of study drug regimen (pre-surgical resection), post-surgical resection

Eligibility Criteria

Male or female participants at least 19 years old.

Inclusion Criteria: - Subjects with biopsy-proven adenocarcinoma of the pancreas - staged by IIb or greater by by EUS, or tumor greater than 2.6 cm on EUS or pancreatic protocol helical CT scan demonstrating venous involvement - Karnofsky performance status >/= 70. - No active second malignancy except for basal cell carcinoma of the skin - Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by: - Serum creatinine level ≤1.5 the upper limits of normal - Serum total bilirubin level ≤1.5 X ULN - White blood cell count >/= 3.5x109/ml per ml and platelet count ≥ 100x109 per ml - Age >18 years. - For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent. - 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 study entry. - Prior use of radiotherapy or investigational agents for pancreatic cancer. - Any evidence of metastasis to distant organs (liver, lung, peritoneum). - Symptomatic or endoscopic evidence of gastric outlet obstruction - Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin - Inability to adhere to study and/or follow-up procedures - History of allergic reactions or hypersensitivity to the study drugs (hydroxychloroquine, gemcitabine). - Other concurrent experimental therapy. - The effects of HCQ, and gemcitabine on the developing human fetus are unknown. For this reason 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 registration to rule out pregnancy. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well. - Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HCQ and gemcitabine is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future. - Due to the risk of disease exacerbation, 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 EKG with 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.

Additional Information

Official title Phase I/II Study of Preoperative Gemcitabine in Combination With Oral Hydroxychloroquine (GcHc) in Subjects With High Risk Stage IIb or III Adenocarcinoma of the Pancreas
Principal investigator Herbert Zeh, MD
Description This is a phase I/II trial designed to assess the safety, tolerability and efficacy of neoadjuvant oral hydroxychloroquine (Plaquenil®) in combination with FDR gemcitabine in subjects with high risk IIb or III adenocarcinoma of the pancreas. Eligible subjects will be administered hydroxychloroquine orally once or twice daily (depending on dose) in combination with FDR gemcitabine (on days 1 and 15) for 31 days prior to surgical resection. Dose escalations of hydroxychloroquine will proceed using Storer's Up-and-Down algorithm D. Subjects will be monitored for side effects and tolerability of the drug. Pre- and post-treatment PET scans will be the primary means to assess response to therapy. Resected tumors will also be assessed for evidence of inhibition of autophagy as well as histopathologic response and margin negative resection and number of positive lymph nodes.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by University of Pittsburgh.