7 research outputs found
CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure
to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched,
with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted
treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need
to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in
the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336
patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be
recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to
epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min
intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab
increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free
survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed
according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and
for other time-to-event endpoints).
Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab
in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely
to become the new standard of care in the UK
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
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.</p
Additional file 1: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
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