An open-label, multicenter, phase III trial of nab-paclitaxel (NP) versus dacarbazine (DTIC) in previously untreated patients (PTs) with metastatic malignant melanoma (MMM).

Abstract

TPS314 Background: Nab-paclitaxel (Abraxane; NP) a Cremophor-free, nanoparticle albumin formulation of paclitaxel targets albumin receptors on tumor cells and is preferentially taken up and retained by cells expressing SPARC (secreted protein acidic and rich in cysteine), an albumin-binding protein. In preclinical and clinical models it has a better safety profile and less toxicity than seen with standard Cremophor formulation of paclitaxel. NP is approved for metastatic breast cancer. In a phase II study of NP in MMM a clinical benefit of 49% and a median survival of 9.6 months was noted in chemotherapy-naïve PTs and 38% and 12.1 months in previously treated PTs. Methods: To determine the efficacy of NP compared to standard therapy with DTIC we have initiated this randomized phase III study. Cytotoxic chemotherapy-naïve PTs with stage IV MMM and typical inclusion and exclusion criteria are randomized to NP, 150 mg/m2 weekly X 3/4 weeks or DTIC 1000 mg/m2 Q 3 W. Dosage reductions of NP to 120 and 90 mg/m2 and of DTIC to 800 and 600 mg/m2 and the use of filgrastim for neutropenic fever are allowed. Assessments of efficacy by CT scans are conducted every 8 weeks in both arms. The primary efficacy endpoint is progression-free survival and the main secondary endpoint is overall survival. Other secondary endpoints include safety and tolerability of the regimens, NP pharmacokinetic parameters, effects of therapy on and the relationship of response to the levels of SPARC and gene methylation, mutational and other biomarkers, response rate, stable disease rate at ≥ 16 weeks and duration of response. The study is planned to randomize 257 PTs per arm (514 total). A total of 104 multinational sites are anticipated and currently 34 are open. The protocol opened in May 2009 and accrual is to be completed in 2010. Currently 60 PTs have been entered on the trial and accrual is on schedule. In summary, this is a registration trial for NP monotherapy as first-line treatment for MMM. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience Abraxis BioScience