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

This study is currently recruiting participants.
Verified October 2013 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01144169
First received: June 10, 2010
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Renal Cell Carcinoma
Drug: Hydroxychloroquine (HC)
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB Study of Hydroxychloroquine Prior to Nephrectomy in Patients With Primary Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Assess the effect of pre-operative HC on phenotype and function of DC and NK cells [ Time Frame: One month post-nephrectomy ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01144169

Contacts
Contact: Jodi K. Maranchie, MD 412-605-3019 maranchiejk@upmc.edu
Contact: Kimberly Jones, RN BSN 412-623-2764

Locations
United States, Pennsylvania
UPCI/UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Principal Investigator: Jodi K. Maranchie, MD         
UPMC Department of Urology Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jodi K Maranchie, MD    412-605-3019      
Contact: Kimberly J Jones, RN BSN    412-623-2764      
Sub-Investigator: Leonard J Appleman, MD PhD         
Sub-Investigator: Michael T Lotze, MD         
Sub-Investigator: Ronald Hrebinko, MD         
Sub-Investigator: Benjamin Davies, MD         
Sub-Investigator: Ronald Benoit, MD         
Sub-Investigator: Jeffrey Gingrich, MD         
Sub-Investigator: Steven Jackman, MD         
Sub-Investigator: Rahul A Parikh, MD, PhD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Jodi K. Maranchie, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01144169     History of Changes
Other Study ID Numbers: UPCI 10-029
Study First Received: June 10, 2010
Last Updated: October 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Renal cell carcinoma
Hydroxychloroquine
Nephrectomy
Autophagy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Hydroxychloroquine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 16, 2014