SAKK 17/16: Lurbinectedin Monotherapy in Pa-tients with Progressive Malignant Pleural Mesothelioma. A Multicenter, Single-arm Phase II Trial

Automatically Closed · 2017 until 2021

Clinical Studies
Multicentric, KSSG as participating partner
Automatically Closed
Start Date
End Date
Brief description/objective

Malignant mesothelioma arises from the mesothelial cells of the pleural, peritoneal or pericardial lining and is often associated with asbestos exposition (Robinson, 2005). There is no cure for most malignant mesotheliomas and the scope of all three major oncological therapeutic procedures (surgery, radiotherapy and chemotherapy) is to re-duce/eliminate symptoms as well as to prolong progression free survival (PFS) and/or overall survival (OS). While pro-gressive patients are still in good health able to undertake a second-line treatment, there is no standard treatment for progressive disease (Ceresoli, 2015). Outside clinical trials commonly used agents are navelbine and gemcitabine either alone or (in a minority of cases) in combination with platinum (Manegold, 2005; Zauderer 2014; Kostron, 2015). However, most of the studies have shown a modest benefit in terms of PFS (and OS), thus the majority of the experts advocate treatment of such patients within clinical trials. Trabectedin has been tested within the ATREUS- single arm multicenter Phase II trial as palliative treatment in pro-gressive mesotheliomas, and recently Cortinovis et al. pre-sented the preliminary results of the sarcomatoid and/or biphasic subgroup, where 5/17 evaluable patients had a sustained time-to-further progression of >4months (Cortinovis, 2015). Lurbinectedin is a novel compound structurally related to trabectedin and with similar mode of action. Pre-clinical data showed a better safety profile than trabectedin (Leal, 2010). Lurbinectedin has been already tested in different Phase I-II trials showing promising activi-ty in ovarian, pancreatic, breast, small and non-small cell lung cancer as well as in other tumor types, with objective responses averaging 30%, disease stabilization up to 75% and having manageable toxicity. Although lurbinectedin has not been widely tested in mesotheliomas, some meso-thelioma patients have been already treated with lurbi-nectedin where again promising activity has been observed (Metaxas, 2016; Calvo, 2012). Aim of this study is to provide the “proof of concept” of efficacy and tolerability of lurbinectedin monotherapy in progressive malignant mesotheliomas.