Mesothelioma Research Programme, Department of Genetics and Genome Biology, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK.
Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
BMJ Open. 2023 Nov 22;13(11):e073120. doi: 10.1136/bmjopen-2023-073120.
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.
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.
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.
ISCRTN16171129; NCT05455424.
恶性间皮瘤是一种快速致命的癌症，在过去三十年中呈流行率上升趋势。间皮瘤的靶向治疗一直缺乏。先前的一项名为 MiST1（NCT03654833）的研究评估了聚（ADP-核糖）聚合酶（PARP）抑制剂在间皮瘤中的疗效。这项研究达到了主要终点，15%的患者的持久缓解超过 1 年。因此，需要评估 PARP 抑制剂在复发间皮瘤患者中的疗效，因为这些患者的选择有限。尼拉帕尼是 NERO 中使用的 PARP 抑制剂。
NERO 是一项多中心、两臂、开放标签的英国随机 2 期临床试验，旨在评估 PARP 抑制剂在复发间皮瘤中的疗效。正在招募 84 名患者。NERO 不受治疗线的限制；然而，合格的参与者必须接受过批准的基于铂的系统治疗。参与者将按照组织学和对先前基于铂的化疗的反应进行 2:1 分层，随机接受活性症状控制（ASC）和尼拉帕尼或 ASC 单独治疗，最长 24 周。参与者将接受治疗，直到疾病进展、退出、死亡或出现严重的治疗限制毒性。随机接受尼拉帕尼的参与者将在 3 周周期内每天服用 200 或 300mg。主要终点是无进展生存期，其中进展由改良实体瘤反应评估标准（mRECIST）或 RECIST 1.1；研究者报告的进展；或任何原因导致的死亡，以先发生者为准。次要终点包括总生存期、最佳总体反应、12 周和 24 周疾病控制、缓解持续时间、治疗依从性和安全性/耐受性。如果 NERO 显示尼拉帕尼安全且具有生物学疗效，它可能会导致未来在复发间皮瘤中进行后期随机对照试验。
该研究于 2022 年 5 月 6 日获得伦敦-汉普斯特德伦理委员会的伦理批准（22/LO/0281）。所有中心的数据将一起进行分析，并尽快发表。
ISCRTN16171129；NCT05455424。
