Hydroxychloroquine in Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery

Early Phase 1

Completed

• Conditions: Melanoma (Skin)
• Interventions: Drug: hydroxychloroquine

• Registration Number: NCT00962845
• Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary

RATIONALE: Studying samples of blood, tumor tissue, and skin in the laboratory from patients with melanoma receiving hydroxychloroquine may help doctors understand the effect of hydroxychloroquine on biomarkers.

PURPOSE: This early phase I trial is studying hydroxychloroquine in patients with stage III or stage IV melanoma that can be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

* To characterize the effects of hydroxychloroquine (HCQ) on the modulation of markers of autophagy, as measured by p62, Beclin1, LC3, and GRp170 expression, in pre- and post-treatment tumor biopsy samples, skin samples, and peripheral blood mononuclear cell samples from patients with stage III or IV melanoma undergoing palliative or curative surgery.

Secondary

* To determine whether the steady-state plasma concentration of HCQ correlates with observed trends in induced markers of autophagy.

* To determine the potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation (Ki-67 and mitotic rate) or an increase in apoptosis (activated caspase-3 and TUNEL assays) in melanoma specimens.

OUTLINE: Patients receive oral hydroxychloroquine twice daily for 14 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Blood, tumor tissue, and skin samples are collected for pharmacokinetic and correlative laboratory studies. Expression of p62, Beclin1, LC3, and GRp170 (autophagy markers) is analyzed.

Study Timeline

• Study First Submitted: 2009-08-19
• Study First Submitted QC: 2009-08-19
• Study First Posted: 2009-08-20
• Study Start: 2010-09
• Primary Completion: 2013-05-30
• Study Completion: 2013-05-30
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-01
• Last Update Posted: 2022-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hydroxychloroquine	hydroxychloroquine	Patients must have tumor accessible for pre-treatment biopsy (see 5.1.2). Patients will be enrolled on the trial, undergo biopsy of their tumors if no banked tumor is available, and then begin an oral dose of HCQ at the dose of 200 mg twice daily. At the end of two weeks the patients will undergo resection of their tumors. HCQ will be given to the patients up to the day of the operation but not resumed postoperatively.

Primary Outcome Measures

Name	Time	Method
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression	1 year

Secondary Outcome Measures

Name	Time	Method
Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy	1 year
Potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation or an increase in apoptosis	1 year

Trial Locations

Locations (1)

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States