Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis

Louis-Emmanuel Chriqui; Etienne Abdelnour-Berchtold; Edoardo Zanfrini; Severine Devesa-Perez; Michel Gonzalez; Thorsten Krueger; Kim Ellefsen; Alice Destaillats; David Bonnet; Martin Hübner; Hasna Bouchaab; Michal Bassani-Sternberg; Solange Peters; Sabrina Cavin; Jean Y Perentes

doi:10.1016/j.ctarc.2024.100858

Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis

Cancer Treat Res Commun. 2024 Dec 17:42:100858. doi: 10.1016/j.ctarc.2024.100858. Online ahead of print.

Authors

Affiliations

¹ Division of Thoracic Surgery, University Hospital of Lausanne, Rue du Bugnon 46 1011, Lausanne, Switzerland.
² Sponsor Research Office (SRO, University Hospital of Lausanne, Rue du Bugnon 46 1011, Lausanne, Switzerland.
³ Division of Visceral Surgery, University Hospital of Lausanne, Rue du Bugnon 46 1011, Lausanne, Switzerland.
⁴ Division of Oncology, University Hospital of Lausanne, Rue du Bugnon 46 1011, Lausanne, Switzerland.
⁵ Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
⁶ Division of Thoracic Surgery, University Hospital of Lausanne, Rue du Bugnon 46 1011, Lausanne, Switzerland. Electronic address: jean.perentes@chuv.ch.

PMID: 39708537
DOI: 10.1016/j.ctarc.2024.100858

Abstract

Background: Pleural carcinosis originates from various cancers. Its management consists in systemic therapies combined to dyspnea relief procedures. Prior studies have tested hyperthermic intrathoracic chemotherapy to treat pleural carcinosis with interesting patient survival results. However, these approaches were limited by local toxicity. Pre-clinical data have shown that hyperthermia combined to local pleural chemotherapy increased the immune response against tumors. Recently, pressurized intraperitoneal aerosol chemotherapies (PIPAC) showed improved cytostatic penetration in abdominal carcinosis with a 10-fold-lower chemotherapy dose and minimal side-effects. This approach was also tested in limited numbers of patients with pleural carcinosis but never combined with hyperthermia.

Methods: Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin (PITHAC) is an open-label dose-escalation phase I trial. Patients with pleural carcinosis, eligible for the surgical management of their pleural effusion can be enrolled. Cisplatin (7.5-12-5-35-70 mg/m2) heated at 39±1 °C is delivered into the thoracic cavity before the surgical effusion management. Initially, the study consists in a dose escalation of the four different cisplatin doses. The primary endpoint is the maximal tolerated dose of cisplatin administered by PITHAC. The secondary and translational endpoints are adverse events and the immune response directed against cancer following PITHAC. There is then an expansion phase at the recommended cisplatin dose on an additional 15 patients with identical outcomes.

Discussion: Pressurized intrathoracic delivery of chemotherapy under hyperthermic conditions was never tested so far. We plan to determine the safety of such an approach in patients managed for pleural carcinosis. If proven safe, PITHAC could be combined with systemic immunotherapies for the management of cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT06281860.

Keywords: Hyperthermic chemotherapy; Intrapleural Chemotherapy; Pleural carcinosis.

Associated data

ClinicalTrials.gov/NCT06281860