Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
BMJ Open. 2023 Jan 30;13(1):e063500. doi: 10.1136/bmjopen-2022-063500.
Immunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC.
The CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment.
This study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal.
EudraCT number: 2018-003461-34.
gov ID NCT05655715.
免疫检查点抑制剂（CPIs）的免疫疗法彻底改变了癌症治疗，但在转移性去势抵抗性前列腺癌（mCRPC）中没有令人信服的效果。有人提出，CPIs 与低分割立体定向体部放射治疗（SBRT）联合使用可能具有协同作用，最近的试验也支持这一观点。我们假设在 CPI 治疗中加入 SBRT 可以提高 mCRPC 患者的反应率。
CheckPRO 试验是一项开放标签、随机、两阶段、二期试验。我们计划招募和随机分配 80 名可评估的 mCRPC 患者，这些患者在接受≥2 线治疗后进展。招募工作于 2019 年 11 月开始，预计招募期为 38 个月。参与者接受治疗 52 周，包括 4 个周期的 ipilimumab 和 nivolumab，联合或不联合同时 SBRT（单次软组织或骨转移 24 Gray，分为 3 次），随后进行 10 个周期的 nivolumab 治疗。参与者随访至进展、死亡或治疗结束后 12 个月。主要终点是客观缓解率和前列腺特异性抗原（PSA）缓解率。次要终点包括安全性、影像学无进展生存期、临床获益率、缓解持续时间、PSA 无进展生存期超过 12 周、生活质量和总生存期。探索性终点包括肿瘤活检和连续血液样本的转化分析。基线、第三次治疗前和治疗结束时采集转移部位的活检。连续在基线和每次影像学评估时进行免疫监测和循环肿瘤 DNA 采血。
本研究遵循赫尔辛基宣言，并获得丹麦伦理委员会系统的批准（期刊号：H-19016100）。所有参与者必须在入组前接受书面和口头信息，并签署知情同意书。研究结果将在国际同行评议期刊上发表。
EudraCT 编号：2018-003461-34。
gov ID NCT05655715。
