Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design.

Autor: Stella, Giulia Maria, Lisini, Daniela, Pedrazzoli, Paolo, Galli, Giulia, Bortolotto, Chandra, Melloni, Giulio, D'Ambrosio, Gioacchino, Klersy, Catherine, Grosso, Amelia, Paino, Francesca, Tomaselli, Stefano, Saracino, Laura, Alessandri, Giulio, Pessina, Augusto, Grignani, Elena, Rosti, Vittorio, Corsico, Angelo Guido, Comoli, Patrizia, Agustoni, Francesco
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Zdroj: Cancers; Oct2024, Vol. 16 Issue 19, p3391, 12p
Abstrakt: Simple Summary: The phase I monocentric PACLIMES trial evaluates the effects of local administration of an innovative tool composed of mesenchymal stromal cells loaded with paclitaxel directly injected in the pleural space in mesothelioma patients in a neoadjuvant setting. The trial explores the safety and toxicity of the drug product, but also an exploratory objective aimed at evaluating its antiproliferative capacity. The results of this study will validate a promising therapeutic option for an unmet clinical need such as pleural mesothelioma and open the way to an efficient management of malignant pleural effusion in case of advanced cancers from different sites of primary origin. Background and rationale. 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, such as the pleural cavity. Study design. 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, including PM, although some limitations are 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 PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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