Pilot early phase II study of decitabine and carboplatin in patients with advanced melanoma

INTRODUCTION: Resistance to targeted and immune checkpoint blockade treatment remains a major problem in patients with advanced metastatic melanoma. To overcome this problem, there needs to be a decrease in burden of disease as well as re-establishing of immune sensitivity. The aim of this early phase 2 clinical trial is to investigate a novel way of sequencing and combining decitabine and carboplatin to decrease methylation and increase DNA repair resulting in a decrease in the disease burden and to re-establish sensitivity to the immune response. METHODS AND ANALYSIS: This single-site early phase 2 clinical trial will be conducted in 30 patients with metastatic melanoma that are resistant to all approved therapies. Patients will receive 2 × 4-week cycles of decitabine 7 mg/m(2) IVI/day for 5 days (D1-D5) followed by Carboplatin AUC 5 IVI on D8; Week 3 and Week 4 no treatment. The primary objective is to determine DNA methylation and DNA repair levels before, and immediately after treatment; quantify immune-response markers (PDL-1, PD-1, CD4/CD8, and CD68) in blood, tumor and microenvironment before treatment and after 2 cycles. The secondary outcome objective is to quantify response rate (RR) to administration of 2 cycles of decitabine and carboplatin cycle using response evaluation criteria in solid tumors (RECIST 1.1) criteria. This data will be used to calculate sample size and determine statistical analysis plan for larger Phase 2 study. ETHICS AND DISSEMINATION: Protocol version 1.1 was reviewed and approved by the Hunter New England Health Human Research Ethics Committee (Reference No: 15/12/16/3.08, NSW HREC Reference No: HREC/15/HNE/505) and site-specific approval from the Calvary Mater Hospital Newcastle, NSW, Australia (NSW SSA Reference No: SSA/16/HNE/224). Primary and secondary outcomes and safety data will be disseminated through publications. TRIAL REGISTRATION DETAILS: Australian New Zealand Clinical Trial Registry ACTRN12616000440426