A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE).
A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE).
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尼拉帕尼加醋酸阿比特龙和泼尼松与醋酸阿比特龙和泼尼松治疗转移性前列腺癌患者的 III 期随机、安慰剂对照、双盲研究 (MAGNITUDE)。
DOI：
10.1200/jco.2020.38.15_suppl.tps5588
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发表时间：
2020
影响因子：
45.3
通讯作者：
S. Sandhu
中科院分区：
文献类型：
--
作者：
K. Chi;D. Rathkopf;G. Attard;Matthew R. Smith;E. Efstathiou;D. Olmos;E. Small;J. Lee;D. Ricci;J. Simon;Xin Zhao;N. Kothari;Shinta Cheng;S. Sandhu
TPS 5588背景：临床前数据表明，当PARP抑制剂（PARPi）Niraparib与雄激素通路抑制剂醋酸阿比特龙联合使用时，具有协同抗肿瘤活性1。在醋酸阿比特龙加泼尼松（AAP）基础上添加PARPi，与单独使用AAP相比，无论DNA修复基因缺陷（DRD）状态如何，mCRPC患者的放射学无进展生存期（rPFS）均有所改善2。一项I期研究的中期结果支持Niraparib 200 mg联合AAP治疗mCRPC 3患者的安全性和耐受性。本III期研究的目的是比较Niraparib + AAP与AAP+安慰剂作为mCRPC一线治疗的疗效和安全性。研究方法：这项正在进行的多中心MAGNITUDE研究（NCT 03748641）将在28个国家的约300家研究中心开放，并将入组除正在进行的雄激素剥夺治疗[ADT]和≤4个月的AAP外未接受转移性去势抵抗治疗的mCRPC患者。DRD状态将通过血浆和组织测定确定。DRD队列（n=400）和无DRD队列（n=600）将分别以1：1的比例随机分配至Niraparib + AAP或安慰剂+ AAP组。首例患者于2019年2月获得知情同意，入组正在进行中。本研究的主要目的是比较各队列和治疗组中通过设盲独立中心放射学审查评估的放射学无进展生存期（rPFS）。为了检验联合治疗相对于AAP的优效性，估计样本量以提供92%的把握度检测DRD队列中HR≤0.65 rPFS，94%的把握度检测无DRD队列中HR≤0.67 rPFS，均在双侧显著性水平0.05。次要目的是症状进展时间、细胞毒化疗时间和总生存期。将评价安全性和药代动力学特征。1Rajendra N，et al. Cancer Res 2019;79（13 Suppl）：Abstract nr 2134. 2Clarke N，et al. Lancet Oncol. 2018;（7）：975-986. 3Saad，et al. Ann Oncol，2018;29（suppl 8），mdy284.043，https://doi.org/10.1093/annonc/mdy284.043）临床试验信息：NCT 03748641。
TPS5588 Background: Preclinical data suggest synergistic antitumor activity when the PARP inhibitor (PARPi) niraparib is combined with the androgen pathway inhibitor abiraterone acetate1. The addition of a PARPi to abiraterone acetate plus prednisone (AAP) showed improved radiographic progression-free survival (rPFS) vs AAP alone in patients with mCRPC regardless of DNA repair gene defect (DRD) status2. Interim results from a phase I study support safety and tolerability of niraparib 200 mg combined with AAP in patients with mCRPC3. The objective of this Phase III study is to compare the efficacy and safety of niraparib plus AAP versus AAP with placebo as first-line therapy for mCRPC. Methods: This ongoing multicenter MAGNITUDE study (NCT03748641) will open in approximately 300 sites across 28 countries and will enroll patients with mCRPC who have not received treatment in the metastatic castrate resistant setting other than ongoing androgen deprivation therapy [ADT] and ≤4 months of AAP. DRD status will be determined by plasma and tissue assays. The cohort with DRD (n=400) and the cohort without DRD (n=600) will each be randomized 1:1 to niraparib + AAP or placebo + AAP. The first patient was consented in February 2019 and enrollment is ongoing. The primary objective of the study is to compare radiographic progression-free survival (rPFS) as assessed by blinded independent central radiology review in each cohort and treatment group. To test superiority of the combination vs AAP, sample sizes were estimated to provide 92% power to detect HR≤0.65 rPFS in the cohort with DRD and 94% power to detect HR≤0.67 in rPFS in the cohort without DRD, both at a 2-tailed level of significance of 0.05. The secondary objectives are time to symptomatic progression, time to cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic profiles will be evaluated. 1Rajendra N, et al. Cancer Res 2019;79(13 Suppl):Abstract nr 2134. 2Clarke N, et al. Lancet Oncol. 2018;(7):975-986. 3Saad, et al. Ann Oncol, 2018;29 (suppl 8), mdy284.043, https://doi.org/10.1093/annonc/mdy284.043 ) Clinical trial information: NCT03748641 .