1542TiP - Vinorelbine in Mesothelioma (VIM): A Randomised Phase II Trial of Oral Vinorelbine as Second-Line Therapy for Patients with Malignant Pleural Mesothelioma (MPM) Expressing Brca1 – a Study in Progress

Abstract

ABSTRACT Background Mesothelioma is increasing worldwide. However there is no approved therapy in the second-line setting. Vinorelbine exhibits promising activity, however there has been no randomised evaluation or validation of biomarkers to support patient stratification. We have recently reported that BRCA-1 is an essential regulator of mesothelioma sensitivity to vinorelbine, and its expression is lost in approximately 38%1. The Cancer Research UK VIM trial is to be sponsored by the University of Leicester in collaboration with the Wales Cancer Clinical Trials Unit. Aims To evaluate the efficacy of second-line vinorelbine plus active symptom control (ASC), versus ASC. Secondary endpoints: tolerability, response rate, change in tumour volume and overall survival. BRCA1 expression IHC will be evaluated as a stratification factor. Methods An open label, randomised trial of weekly vinorelbine 80mg/m2 plus ASC versus ASC alone. The control arm of ASC will be defined by local practice. Both study arms will be continued until documented evidence of radiological progression or unacceptable toxicity. The sample size has been calculated using the parameters; α = 0.2, β = 0.1 (90% power), hazard ratio 0.65, 1-sided logrank test and 2:1 randomisation favouring vinorelbine. This requires recruitment of 114 patients. However, as we hypothesis that BRCA-1 expression is required for vinorelbine activity and have estimated its absence in one third of patients, the sample size may be inflated to 171 patients depending on the results of an interim analysis. We aim to open the study in Q1 2013 and recruit over 18 months. The results of this study will be used to inform the design of a future phase III study, with stratification of patients to optimise efficacy. BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma. Busacca S et al J Pathol. 2012 Jun; 227(2):200-8 Disclosure All authors have declared no conflicts of interest.