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
- 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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
Janice M. Mehnert, MD
Cancer Institute of New Jersey
United States: Institutional Review Board
|The Cancer Insitute of New Jersey||New Brunswick, New Jersey 08901|