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

NCT00962845 | Completed Early Phase 1

• 5 other identifiers: 0220090117P30CA072720CDR0000648156NCI-2011-03324090901
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma (Skin)

Keywords

stage III melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression

  1 year

Secondary Outcomes (2)

• 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

Study Arms (1)

Hydroxychloroquine

EXPERIMENTAL

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.

Drug: hydroxychloroquine

Interventions

hydroxychloroquine DRUG

200 mg twice daily in the first ten patients. If the first ten patients tolerate this dosage schedule (200 mg bid) without significant side effects (Grade 3 or greater gastrointestinal upset, skin toxicity, myopathy or any visual disturbances whatsoever), the second ten patients will be enrolled at a dose of 400 mg bid

Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed melanoma * Stage III or IV disease * Has ≥ 2 resectable tumors OR tumor large enough to undergo pre-treatment core needle biopsy * Must be a candidate for curative or palliative surgical resection of disease * Brain metastases allowed provided they were previously treated and have been stable for \> 2 weeks PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute granulocyte count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * SGOT and SGPT \< 2.5 times upper limit of normal (ULN) * Negative pregnancy test * Fertile patients must use effective contraception * No history of any social or medical condition that, in the opinion of the investigator, may interfere with the patient's ability to comply with the study or pose additional or unacceptable risk to the patient * No concurrent serious systemic disorder that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study * No active clinically significant infection requiring antibiotics * No hypertension that cannot be controlled by medication (i.e., diastolic blood pressure \> 100 mm Hg despite optimal medical therapy) * No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained in the normal range with medication * No known HIV positivity * No psoriasis or porphyria * No known hypersensitivity to 4-aminoquinoline compounds * No retinal or visual field changes from prior 4-aminoquinoline compound use * No known G-6P deficiency * No known gastrointestinal pathology that would interfere with drug bioavailability * No known prior hypersensitivity to hydroxychloroquine or any of its components * No clinically significant bleeding or clotting disorder that would preclude curative or palliative surgery PRIOR CONCURRENT THERAPY: * Recovered from prior therapy * More than 2 weeks since prior cytotoxic or biologic agents (6 weeks for mitomycin or nitrosoureas) * At least 2 weeks since prior surgery, radiotherapy, hormonal therapy, or other drug therapy for melanoma * No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus * No concurrent disease-modifying anti-rheumatic drugs * No concurrent hydroxychloroquine for treatment or prophylaxis of malaria * No concurrent aurothioglucose or antimalarial agents * No other concurrent chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or surgery for cancer * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Janice M. Mehnert, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2009
• First Posted: August 20, 2009
• Study Start: September 1, 2010
• Primary Completion: May 30, 2013
• Study Completion: May 30, 2013
• Last Updated: September 7, 2022

Record last verified: 2022-09

Locations

US (1)