Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma.

Abstract

Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity. Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS). Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%). This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.