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

Primary Purpose

Melanoma (Skin)

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
hydroxychloroquine
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage III melanoma, stage IV melanoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rutgers Cancer Institute of New Jersey

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hydroxychloroquine

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 19, 2009
Last Updated
September 1, 2022
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT00962845
Brief Title
Hydroxychloroquine in Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery
Official Title
A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
May 30, 2013 (Actual)
Study Completion Date
May 30, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
stage III melanoma, stage IV melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
hydroxychloroquine
Intervention Description
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
Primary Outcome Measure Information:
Title
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy
Time Frame
1 year
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janice M. Mehnert, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

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

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