CCI-779 in metastatic melanoma: A phase II trial of the California Cancer Consortium

7523 Background: CCI-779 mTOR kinase inhibitor is a targeted chemotherapeutic agent that inhibits malignant cell cycle progression by binding to FK506-binding protein-12 and forming a complex that interacts with the “mammalian target of rapamycin” (mTOR), resulting in inhibition of signal transduction pathways required for progression through the G1 phase of the cell cycle. CCI-779 has demonstrated activity against melanoma in preclinical models and shown clinical benefit in breast and renal cancer. CCI-779 is not immunosuppressive when administered on an intermittent schedule, and its toxicities are modest, consisting of nausea, diarrhea, hypertriglyceridemia, thrombocytopenia, asthenia and follicular dermatitis. Methods: This trial was designed to detect a median time to progression of >18 weeks in metastatic (mets) melanoma patients (pts) treated with CCI-779, 250 mg intravenously weekly after diphenhydramine premedication. Pts had measurable disease, ≤ one prior chemotherapy regimen for mets, normal organ function. Exclusions: CNS mets, cytochrome P450-inducing or -suppressing drugs, hypertriglyceridemia. Results: 33 pts (21 male), PS 0/1/≥2=17/10/6, 21 previously-treated with chemo- and/or biological agents. One pt had a partial response (4+ months) and remains on therapy. The median time to progression and overall survival were 10 weeks and 5 months, respectively. Toxicities were mild, consisting of mucositis (1 grade [gr] 3, 8 gr 2), diarrhea (2 gr 3), and rash (1 gr 3, 4 gr 2). Hyperlipidemia was cumulative and managed with lipid-lowering agents, rarely requiring treatment delay or dose adjustments. Conclusions: CCI-779 is not sufficiently active in melanoma to warrant further testing as a single agent. Support: Phase II NO1 CM17101 No significant financial relationships to disclose.