- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01144169
Study of Hydroxychloroquine Before Surgery in Patients With Primary Renal Cell Carcinoma
October 24, 2016 updated by: Jodi Maranchie, University of Pittsburgh
A Phase IB Study of Hydroxychloroquine Prior to Nephrectomy in Patients With Primary Renal Cell Carcinoma
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Department of Urology
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Pittsburgh, Pennsylvania, United States, 15232
- UPCI/UPMC Cancer Centers
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Hydroxychloroquine (HC)
HC orally for 14 days prior to nephrectomy
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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)
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Pre-hydroxychloroquine (HC), post-HC/pre-nephrectomy, post-nephrectomy (up to 1 month)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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One month post-nephrectomy
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Assess the effect of pre-operative HC on phenotype and function of DC and NK cells
Time Frame: One month post-nephrectomy
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One month post-nephrectomy
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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
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One month post-nephrectomy
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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)
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Pre-HC, post-HC/pre-nephrectomy, post-nephrectomy (1 month)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jodi K. Maranchie, MD, University of Pittsburgh Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (Actual)
September 1, 2016
Study Completion (Actual)
September 1, 2016
Study Registration Dates
First Submitted
June 10, 2010
First Submitted That Met QC Criteria
June 14, 2010
First Posted (Estimate)
June 15, 2010
Study Record Updates
Last Update Posted (Estimate)
October 26, 2016
Last Update Submitted That Met QC Criteria
October 24, 2016
Last Verified
October 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Hydroxychloroquine
Other Study ID Numbers
- 10-029
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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