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A Phase IB Study of Hydroxychloroquine Prior to Nephrectomy in Patients With Primary Renal Cell Carcinoma

Phase 1
19 Years
Open (Enrolling)
Renal Cell Carcinoma

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Trial Information

A Phase IB Study of Hydroxychloroquine Prior to Nephrectomy in Patients With Primary Renal Cell Carcinoma

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.

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

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

- 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

- 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

- 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.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

Jodi K. Maranchie, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Institutional Review Board

Study ID:

UPCI 10-029



Start Date:

October 2010

Completion Date:

July 2014

Related Keywords:

  • Renal Cell Carcinoma
  • Renal cell carcinoma
  • Hydroxychloroquine
  • Nephrectomy
  • Autophagy
  • Carcinoma
  • Carcinoma, Renal Cell



UPCI/UPMC Cancer Centers Pittsburgh, Pennsylvania  15232
UPMC Department of Urology Pittsburgh, Pennsylvania  15232