Gemcitabine Hydrochloride and Hydroxychloroquine Before Surgery in Treating Patients With High Risk Stage IIB-III Pancreatic Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase II, Phase ITreatment19 and over09-122
NCI-2011-02492, NCT01128296

Trial Description

Summary

The primary goal of our research study is to determine whether treating patients with pancreatic cancer with hydroxychloroquine in combination with gemcitabine (gemcitabine hydrochloride) before surgery is safe. The secondary goal is to determine if this new treatment regimen can effectively treat pancreatic cancer.

Further Study Information

PRIMARY OBJECTIVES:

I. 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.

II. 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.

III. To establish the potential biological activity and suitability for phase II study of GCHC by radiographic tumor response, as assessed by fludeoxyglucose F 18 positron emission tomography (F-18 FDG PET).

SECONDARY OBJECTIVES:

I. Determine the effects of hydroxychloroquine on the plasma pharmacokinetics and metabolism of gemcitabine.

II. Biomarker response (cancer antigen 19-9 [Ca 19-9]), antibodies to cardiolipin, soluble major histocompatibility complex (MHC) class I-related chain A (sMICA) levels.

III. Correlate the level of autophagy in resected pancreatic adenocarcinomas with measures of clinical outcome, histopathologic response and (18F)-FDG PET.

IV. Correlate the levels of autophagic markers in peripheral blood mononuclear cells with histopathologic response and changes in the (18F)-FDG PET activity.

V. Assess coagulation parameters during the protocol treatment.

OUTLINE: This is a phase I, dose-escalation study of hydroxychloroquine followed by a phase II study.

Patients receive hydroxychloroquine orally (PO) once daily (QD) or twice daily (BID) for 28-31 days before surgery. Beginning 48 hours after initiation of hydroxychloroquine, patients receive gemcitabine hydrochloride intravenously (IV) over 100-150 minutes every other week before surgery.

After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 1 year, and then every 4 months thereafter.

Eligibility Criteria

Inclusion Criteria:

Staged by IIb or greater by endoscopic ultrasound (EUS), or tumor greater than 2.6 cm on EUS or pancreatic protocol helical computed tomography (CT) scan demonstrating venous involvement

No active second malignancy except for basal cell carcinoma of the skin

Serum creatinine level =< 1.5 the upper limits of normal

Serum total bilirubin level =< 1.5 X upper limit of normal (ULN)

White blood cell count >= 3.5 x 10^9/ml per ml

Platelet count >= 100 x 10^9 per ml

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

Subjects with biopsy-proven adenocarcinoma of the pancreas

Karnofsky performance status >= 70 or Eastern Cooperative Oncology Group (ECOG) 0, 1

Exclusion Criteria:

Subjects who have received chemotherapy within 12 months prior to study entry

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)

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, human immunodeficiency virus (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 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

Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection

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

Other concurrent experimental therapy

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Pittsburgh Cancer Institute (UPCI)

  • National Cancer Institute
Herbert John Zeh, Principal Investigator

Trial Sites

U.S.A.

Pennsylvania
Pittsburgh

University of Pittsburgh Cancer Institute (UPCI)

Herbert John Zeh
Ph: 412-692-2852
Email: zehh@upmc.edu

Herbert John Zeh
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01128296

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.