Oligometastatic Directed Radiotherapy for Patients With Castration Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- NEST-FS
研究概览
简要总结
In patients with metastatic prostate cancer (PCa) who receive androgen deprivation therapy (ADT), the sensitivity to castration will eventually disappear due to the selection of castration-refractory clones. This will lead to the stage of metastatic castration-refractory prostate can-cer (mCRPC), which is incurable and results in a median overall survival of 2-3 years.
Treatment options for patients with mCRPC include several systemic agents, such as andro-gen receptor-targeted agents (ARTA), chemotherapy (docetaxel, cabazitaxel) and bone-targeting agents (radium- 223). Clinical progression and, to a lesser extent, biochemical pro-gression traditionally imply a switch to the next line systemic treatment (NEST). Within patients with mCRPC, there is a subgroup showing oligo-progression, defined as the progression of up to 3 lesions, including both metastatic and/or local relapse. Oligoprogression reflects a heterogeneous treatment response, which, in turn, reflects the heterogeneity of the clonogenic cells that give rise to mCRPC. Retrospective studies suggest that metastasis-directed radiotherapy (MDRT) to these oligoprogressive lesions delayed the need for NEST. Recently, promising results were published on the use of MDRT in the oligopro-gressive mCRPC (omCRPC) setting, with a NEST-free survival (NEST-FS) of 21 months in well selected patients. Currently, in The Netherlands, patients with omCRPC are frequently referred and treated with MDRT, but a clear treatment protocol and inclusion/selection criteria are missing. Moreover, the exact benefit of MDRT in patients with omCRPC remains unclear, as prospective evi-dence for MDRT in omCRPC is lacking.
详细描述
The primary aim of this study is to test the hypothesis that the addition of MDRT to standard of care (ADT or ADT + chemotherapy or ARTA) in well-selected PCa patients with oligometastatic progressive disease, defined on PSMA PET, prolongs the radiological progression-free survival (rPFS) and postpones the start of next line systemic therapy (NEST). Patients included in this study already have an indication to start NEST, and any delay introduced by adding MDRT will result in a net benefit for the patients.
Primary objectives include: Postponement of the start of next line systemic treatment (NEST), and enhancement of the radiological progression-free survival (rPFS) In this single arm multicenter prospective phase II trial, we aim to include 35 patients with omCRPC (1-3 metastases and/or local recurrence) who will be treated with MDRT to the visible progressive lesions (up to max of 3). Progression is based on PSMA PET.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adenocarcinoma of the prostate.
- •mCRPC setting, with testosterone level < 50 ng/dl or 1.7 nmol/l.
- •Oligoprogressive disease diagnosed on PSMAscan; defined as the progression of pre-existing metastatic disease, and/or the appearance of new metastases and/or the appearance of a local relapse with a maximum of 3 lesions in total.
- •Patients currently treated with ADT, whether combined with another systemic treatment such as ARTA, chemotherapy.
- •For patients treated with chemotherapy, the course should be completed or stopped before start MORT - In case of treatment with ARTA, a minimal of 3 months response (PSA or clinical response).
- •WHO performance status 0-
- •Age > = 18 years old.
- •Patiënt should be presented at the multidisciplinary tumor board of the local hospital in which the therapy will be given.
- •Before patiënt registration, written informed consent must be given according to ICH/GCO and national/local regulations.
排除标准
- •Serum testosterone level > 50 ng/ml or > 1.7 nmol/l.
- •Presence of more than 3 progressive/new metastatic lesions and/or local recurrence (which counts for 1 lesion).
- •Active malignancy other than prostate cancer that can potentially interfere with the interpretation of the trial, except non-melanoma skin cancer or non-invasive urothelial cell carcinoma.
- •Local recurrence in the prostate after previous radiotherapy
- •Previous treatments (RT, surgery) or comorbidities making new treatment with MDRT impossible.
- •Disorder precluding understanding of trial Information or informed consent or signing informed consent.
- •Evidence of PSMA-negative disease.
研究组 & 干预措施
MDRT to oligoprogression
Patients included in the study with a post prostatectomy local recurrence on the PSMA PET with up to 3 oligometastases will be treated preferably with SBRT to all oligometastatic lesions and to the local recurrence in prostate bed
干预措施: Metastasis directed radiotherapy (Radiation)
结局指标
主要结局
NEST-FS
时间窗: 6, 12-and 24-months
Next line systemic treatment free survival
rPFS
时间窗: 6, 12-and 24-months
radiologic progression free survival
次要结局
- Biochemical progression(From date of randomization until the date of first documented biochmical progression, assessed up to 36 months)
- Overall survival (OS)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
- Quality of life (QoL)(baseline, 6 months, 12 months, 24 months)
- Late grade ≥ 2 gastrointestinal toxicity(Up to 2 years after completion of the RT)
- Acute grade ≥ 2 gastrointestinal toxicity(Up to 3 months after completion of the RT)
- Acute grade ≥ 2 genitourinary toxicities(Up to 3 months after completion of the RT)
- Quality of Life (QoL)(baseline, 6 months, 12 months, 24 months)
- Late grade ≥ 2 genitourinary toxicities(Up to 2 years after completion of the RT)
- Late grade ≥ 2 genitourinary toxicity(Up to 2 years after completion of the RT)