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A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma

Phase 0
18 Years
Open (Enrolling)
Melanoma (Skin)

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Trial Information

A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma



- 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.


- 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

Inclusion Criteria


- 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


- 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


- Recovered from prior therapy

- More than 2 weeks since prior cytotoxic or biologic agents (6 weeks for mitomycin or

- 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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Janice M. Mehnert, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Institutional Review Board

Study ID:




Start Date:

September 2010

Completion Date:

June 2013

Related Keywords:

  • Melanoma (Skin)
  • stage III melanoma
  • stage IV melanoma
  • Melanoma



The Cancer Insitute of New Jersey New Brunswick, New Jersey  08901