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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01144169
Recruitment Status : Terminated (barriers to accrual: delay until surgery and additional pre-operative visits)
First Posted : June 15, 2010
Last Update Posted : October 26, 2016
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Jodi Maranchie, University of Pittsburgh

Study Description
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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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Hydroxychloroquine (HC) Phase 1

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IB Study of Hydroxychloroquine Prior to Nephrectomy in Patients With Primary Renal Cell Carcinoma
Study Start Date : October 2010
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Hydroxychloroquine (HC)
HC orally for 14 days prior to nephrectomy
 Drug: 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.
Other Name: Plaquenil®


Outcome Measures
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Primary Outcome Measures :
  1. Measure biologic markers of autophagy in tumor and normal tissues (peripheral blood mononuclear cells, renal parenchyma) following a short course of pre-operative oral hydroxychloroquine [HC] in patients with renal cell carcinoma. [ Time Frame: Pre-hydroxychloroquine (HC), post-HC/pre-nephrectomy, post-nephrectomy (up to 1 month) ]

Secondary Outcome Measures :
  1. Measure the serum biomarker response (HMGB1, sRAGE, VEGF, fibronectin, CRP, IL-6, nicotinamide N-methyltransferase, thrombospondin-1, CD 14, and ferritin) following pre-operative oral HC. [ Time Frame: One month post-nephrectomy ]
  2. Assess the effect of pre-operative HC on phenotype and function of DC and NK cells [ Time Frame: One month post-nephrectomy ]
  3. Assess the effect of pre-operative HC on abundance of neutrophils, NK cells, T-cells and T-cell subsets, PDCs and MDCs in the resected tumor, expression of CAIX and NOX4 compared with matched age/sex/histology matched controls. [ Time Frame: One month post-nephrectomy ]
  4. Assess miRNAs pre and post HC and postoperatively in blood and in resected tumor and normal kidney compared to stage- and grade-matched controls. [ Time Frame: Pre-HC, post-HC/pre-nephrectomy, post-nephrectomy (1 month) ]

Eligibility Criteria
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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01144169


Locations
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United States, Pennsylvania
UPCI/UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
UPMC Department of Urology
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Jodi K. Maranchie, MD University of Pittsburgh Medical Center
More Information
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Responsible Party: Jodi Maranchie, MD, FACS, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01144169    
Other Study ID Numbers: 10-029
First Posted: June 15, 2010    Key Record Dates
Last Update Posted: October 26, 2016
Last Verified: October 2016
Keywords provided by Jodi Maranchie, University of Pittsburgh:
Renal cell carcinoma
Hydroxychloroquine
Nephrectomy
Autophagy
Additional relevant MeSH terms:
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Hydroxychloroquine
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents