Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres.

Autor:	Fennell D; Mesothelioma Research Programme, Department of Genetics and Genome Biology, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK., Griffiths D; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK dpg1e20@soton.ac.uk., Eminton Z; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Morgan-Fox A; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Hill K; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Ewings S; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Stuart C; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Johnson L; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Mallard K; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Nye M; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK., Darlison L; Mesothelioma Research Programme, University Hospitals of Leicester NHS Trust, Leicester, UK., Dulloo S; Department of Genetics and Genome Biology, University Hospitals of Leicester NHS Trust, Leicester, UK., Cave J; Department of Oncology, Wessex NET group ENETS Centre of Excellence, University Hospital Southampton NHS Foundation Trust, Southampton, UK., Luo JL; Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Taylor P; Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK., Spicer J; Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Poile C; Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Bzura A; Leicester Cancer Research Centre, University of Leicester, Leicester, UK., Griffiths G; Southampton Clinical Trials Unit, University of Southampton, Southampton, UK.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2023 Nov 22; Vol. 13 (11), pp. e073120. Date of Electronic Publication: 2023 Nov 22.
DOI:	10.1136/bmjopen-2023-073120
Abstrakt:	Background: Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primary endpoint with 15% of patients having durable responses exceeding 1 year. Therefore, there is a need to evaluate PARP inhibitors in relapsed mesothelioma patients, where options are limited. Niraparib is the PARP inhibitor used in NERO. Methods: NERO is a multicentre, two-arm, open-label UK randomised phase II trial designed to evaluate the efficacy of PARP inhibition in relapsed mesothelioma. 84 patients are being recruited. NERO is not restricted by line of therapy; however, eligible participants must have been treated with an approved platinum based systemic therapy. Participants will be randomised 2:1, stratified according to histology and response to prior platinum-based chemotherapy, to receive either active symptom control (ASC) and niraparib or ASC alone, for up to 24 weeks. Participants will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Participants randomised to niraparib will receive 200 or 300 mg daily in a 3-weekly cycle. The primary endpoint is progression-free survival, where progression is determined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or RECIST 1.1; investigator reported progression; or death from any cause, whichever comes first. Secondary endpoints include overall survival, best overall response, 12-week and 24 week disease control, duration of response, treatment compliance and safety/tolerability. If NERO shows niraparib to be safe and biologically effective, it may lead to future late phase randomised controlled trials in relapsed mesothelioma. Ethics and Dissemination: The study received ethical approval from London-Hampstead Research Ethics Committee on 06-May-2022 (22/LO/0281). Data from all centres will be analysed together and published as soon as possible. Trial Registration Number: ISCRTN16171129; NCT05455424. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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