Phase I clinical trial on pleural mesothelioma using neoadjuvant local administration of paclitaxel loaded mesenchymal stromal cells (PACLIMES trial): rationale and study design

Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, as the pleural cavity. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX) which is widely used in the treatment of different types of solid tumors, among which PM although some limitations related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor surrounding context. The primary objective of the study is to evaluate safety and toxicity of local administration of Paclimes in chemonaive patients, candidates to pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity.