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

Our plain-English summary of 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, by D. Fennell, D. Griffiths, Z. Eminton, et al (BMJ Open, 2023).

The study

• Authors: D. Fennell, D. Griffiths, Z. Eminton, A. Morgan-Fox, K. Hill, S. Ewings, C. Stuart, L. Johnson, K. Mallard, M. Nye, L. Darlison, S. Dulloo, J. Cave, J.L. Luo, P. Taylor, J. Spicer, C. Poile, A. Bzura, G. Griffiths
• Journal: BMJ Open
• Published: 2023;13(11):e073120
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 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.

In plain English

This article was a study protocol. It described a clinical trial, called NERO, that opened to recruitment in July 2022, and it reported no results. NERO was designed as a randomised phase II trial in the UK comparing the drug niraparib plus active symptom control with active symptom control alone. Active symptom control meant standard supportive care such as specialist follow-up, palliative radiotherapy and steroids. The trial was to enrol 84 adults with mesothelioma of any subtype (epithelioid, biphasic or sarcomatoid) and any site, including pleural or peritoneal. All had to have previously received platinum-based therapy and had their disease progress. Patients were to be assigned 2 to 1 in favour of niraparib. Niraparib was to be given at a starting dose of 200 mg once daily, or 300 mg for some patients, for up to 24 weeks. The main planned measure was progression-free survival. The authors hypothesised that niraparib would be tolerable and work better than symptom control alone. They noted that CT scans would not be reviewed centrally and that the trial was not placebo controlled.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for a multicentre, randomised (2:1), open-label phase II trial. The planned primary endpoint was progression-free survival. No results were reported.
• Who was studied: 84 planned adult patients with mesothelioma of any histological subtype and any site (pleural or peritoneal), at approximately 10 UK secondary care hospitals. All had previously received platinum-based systemic therapy. Recruitment opened 11 July 2022 and was planned to end 31 December 2023.
• Exposure: The exposure studied was the drug niraparib, not asbestos. Niraparib was to be taken by mouth at a starting dose of 200 mg once daily (300 mg for patients weighing 77 kg or more with a baseline platelet count of 150×10^9/L or more), in three-weekly cycles for up to 24 weeks, plus active symptom control. The comparison group was to receive active symptom control alone.
• The authors' conclusion: The authors hypothesised that niraparib in patients whose disease had relapsed would be tolerable and would show better efficacy than active symptom control.
• Limitations the authors state:
  • There was no central review of CT scans, which could make tumour response reporting inconsistent across sites.
  • The trial was not placebo controlled, and patients may expect the treatment group to benefit more.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Systemic Therapy, Histology, Chemotherapy, Disease Progression, Progression-Free Survival, Modified RECIST (mRECIST), Overall Survival.

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