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

NCT01144169 | Terminated Phase 1 DMC

• 1 other identifier: 10-029
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Cell Carcinoma

Keywords

Renal cell carcinoma; Hydroxychloroquine; Nephrectomy; Autophagy

Outcome Measures

Primary Outcomes (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.

  Pre-hydroxychloroquine (HC), post-HC/pre-nephrectomy, post-nephrectomy (up to 1 month)

Secondary Outcomes (4)

• 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.

  One month post-nephrectomy

• Assess the effect of pre-operative HC on phenotype and function of DC and NK cells

  One month post-nephrectomy

• 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.

  One month post-nephrectomy

• Assess miRNAs pre and post HC and postoperatively in blood and in resected tumor and normal kidney compared to stage- and grade-matched controls.

  Pre-HC, post-HC/pre-nephrectomy, post-nephrectomy (1 month)

Study Arms (1)

Hydroxychloroquine (HC)

EXPERIMENTAL

HC orally for 14 days prior to nephrectomy

Drug: Hydroxychloroquine (HC)

Interventions

Hydroxychloroquine (HC) 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.

Also known as: Plaquenil®

Hydroxychloroquine (HC)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institutes of Health (NIH): collaborator

Study Sites (2)

UPCI/UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Department of Urology

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; 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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jodi K. Maranchie, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FACS

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: June 15, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

US (2)