Abstract 254TiP
Background
Pleural carcinosis originates from various cancers. Its management consists in systemic palliative therapies combined to dyspnea relief procedures. Prior studies have shown limited activity of normo/hypethermic intrathoracic chemotherapy to treat pleural carcinosis. These approaches could not be generalized because of restricted cytostatic penetration in tumors and local toxicity. Preclinical data demonstrate that hyperthermia combined to local pleural chemotherapy induces an immunogenic response directed against cancer that could be further enhanced by immunotherapy. Recently, pressurized intraperitoneal aerosol chemotherapies (PIPAC) have shown high cytostatic penetration in abdominal carcinosis with low drug concentration requirements and a good safety profile. This approach was tested in small number of patients with pleural carcinosis but never combined with hyperthermia.
Trial design
Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin (PITHAC) is an open-label phase I trial. Patients with proven pleural carcinosis sensitive to cisplatin, a good performance status (ECOG 0-2) and a planned surgical management of their pleural effusion (chemical pleurodesis or indwelling catheter placement by video assisted thoracoscopy) are eligible. Chemotherapy (Cisplatin Teva®) heated at 39 ± 1°C is delivered in the thoracic cavity at a pressure of 8 mmHg for 30 minutes before the surgical effusion management. The first part consists in a dose escalation study (3+3 design) of four cisplatin doses (7.5 – 12.5 – 35 and 70 mg/m2 of body surface). The primary endpoint is the maximum tolerated dose of cisplatin administered by PITHAC. The secondary endpoints are safety as well as, dyspnea and pleural effusion index evaluation after PITHAC. The translational endpoints consist in the blood pharmacokinetics and tumor distribution of cisplatin as well as the immune response landscape (effector T cells directed against tumor neoantigens) after PITHAC. The second part is an expansion phase at the RP2D cisplatin dose on an additional 15 patients.
Clinical trial identification
Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis (BASEC number 2023-00099).
Legal entity responsible for the study
Centre Hospitalier Universitaire Vaudois.
Funding
Fondation chercher trouver.
Disclosure
J.Y. Perentes: Non-Financial Interests, Personal, Advisory Board: BMS, AstraZeneca; Non-Financial Interests, Personal, Training: Johnson and Johnson. M. Gonzalez: Non-Financial Interests, Personal, Training: Johnson and Johnson, Medtronic. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A:MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee Sapphire: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase I/II trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. All other authors have declared no conflicts of interest.