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

This study has suspended participant recruitment.
(Interim analysis)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier:
NCT00962845
First received: August 19, 2009
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Drug: hydroxychloroquine
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation or an increase in apoptosis [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: September 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: hydroxychloroquine
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00962845

Locations
United States, New Jersey
The Cancer Insitute of New Jersey
New Brunswick, New Jersey, United States, 08901
Sponsors and Collaborators
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Janice M. Mehnert, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier: NCT00962845     History of Changes
Other Study ID Numbers: 090901, P30CA072720, CDR0000648156
Study First Received: August 19, 2009
Last Updated: August 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
stage III melanoma
stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 22, 2014