Study of Hydroxychloroquine Before Surgery in Patients With Primary Renal Cell Carcinoma

NCT ID: NCT01144169

Last Updated: 2016-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2016-09-30

Brief Summary

The main goal of this research study is to determine whether treating patients with renal cell cancer with hydroxychloroquine before surgery can make the cancer easier to kill. Another goal is to see how the study drug affects the body's immune cells which fight cancer cells.

Detailed Description

Autophagy is a cellular survival mechanism that protects from stress-induced programmed death. Autophagy may enable renal cancer to escape from cytokine therapy, cytotoxic chemotherapy or targeted agents. Hydroxychloroquine prevents autophagy by blocking acidification of lysosomes, and is being studied in clinical trials as a means of enhancing of cancer therapy. This phase Ib clinical trial will test the hypothesis that pre-operative exposure to HC reduces biologic markers of autophagy in peripheral blood, normal kidney and renal cancer specimens obtained at the time of nephrectomy. These data will be used in the design and pharmacodynamic monitoring of future therapeutic trials of HC in combination with high dose interleukin-2 and other systemic therapies for advanced RCC.

Conditions

Renal Cell Carcinoma

Keywords

Renal cell carcinoma; Hydroxychloroquine; Nephrectomy; Autophagy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hydroxychloroquine (HC)

HC orally for 14 days prior to nephrectomy

Group Type: EXPERIMENTAL

Hydroxychloroquine (HC)

Intervention Type: DRUG

Subjects will receive HC orally for 14 days prior to surgery. The fixed dose of HC will be 400 mg/day in divided doses (200 mg bid). The final dose will be administered on the evening prior to nephrectomy.

Interventions

Hydroxychloroquine (HC)

Subjects will receive HC orally for 14 days prior to surgery. The fixed dose of HC will be 400 mg/day in divided doses (200 mg bid). The final dose will be administered on the evening prior to nephrectomy.

Intervention Type: DRUG

Other Intervention Names

Plaquenil®

Eligibility Criteria

Inclusion Criteria

• Subjects with suspected primary or metastatic RCC (stage 1-IV) with planned nephrectomy or partial nephrectomy.
• ECOG performance status ≤1
• Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by:

• Serum creatinine level ≤1.5 the upper limits of normal (ULN)
• Serum total bilirubin level ≤1.5 X ULN
• White blood cell count > or = 3.5x109/ml per ml and platelet count ≥ 100x109 per ml
• Age >18 years.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Subjects who have received chemotherapy for any diagnosis within 12 months prior to study entry.
• Prior use of radiotherapy or investigational agents for RCC.
• Concurrent malignancies with evidence of active or measurable disease except non-melanoma skin cancer
• Inability to adhere to study and/or follow-up procedures
• History of allergic reactions or hypersensitivity to the study drug (hydroxychloroquine) or current therapy with the study drug for other reasons.
• Other concurrent experimental therapy.
• The effects of HC 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.
• HIV-positive patients are not excluded from the study. However, for patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HC is unknown. Therefore, HIV-positive patients actively receiving anti-retroviral therapy are excluded from the study.
• 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. Hydroxychloroquine is known to affect the CYP2D6 metabolic pathway. A list of drugs with potential interaction is included in Appendix H.
• Patients with previously documented macular degeneration or diabetic retinopathy are excluded.
• Patients with known glucose-6-phosphate dehydrogenase (GP6D) deficiency
• EKG with QTc >500 msec at baseline (average of 3 determinations at 10 minutes interval). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Jodi Maranchie

MD, FACS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jodi K. Maranchie, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

Locations

UPCI/UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

UPMC Department of Urology

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

10-029

Identifier Type: -

Identifier Source: org_study_id