Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 118
- 试验地点
- 7
- 主要终点
- Failure free survival
研究概览
简要总结
The study is an open label, multi-centre, randomized phase III study. The patients will be randomised in a 1:1 ratio to treatment consisting of
- Arm A: MD-SBRT in addition to standard treatment
- Arm B: Standard treatment
Study population: Patients with hormone sensitive prostate cancer (HSPC) with oligometastatic disease detected by PSMA-PET/DT. This includes patients with de novo oligometastatic HSPC and recurrent HSPC after primary RT or prostatectomy.
Primary endpoint: Failure free survival
Secondary endpoints:
- Predictive value of investigated biomarkers in blood and imaging
- Acute and late toxicity after MD-SBRT
- PROM at 3 months, 1, 3 and 5 years
- Castration resistant prostate cancer, CRPC
- Overall survival
- Differences in outcome between patients by strata
Stratification: To avoid imbalance between treatment arms the minimisation method will be used to achieve balance between de novo oligo-metastatic and oligo-recurrent patients, as well as treatment site.
Safety evaluation: Adverse events and side effects graded according to CTCAE v5.0 will be collected every 6th month. Serious Adverse Events are to be reported within 24 hours throughout the study duration.
Statistical methods: Survival endpoints will be calculated using the Kaplan-Meier method with differences compared using the stratified log-rank test. Randomization time is set as baseline time. Pre-planned subgroup analysis will occur based on pre-specified stratification variables. A Cox multivariable regression model will be used to determine factors predictive of survival. Safety analysis will be performed with Mann-Whitney U-test or Fishers exact test.
Criteria for evaluation: Per protocol (patients that have started study treatment) and Intention to treat (all included patients).
Planned sample size: 118 patients
Analysis plan:
The primary end point will be analysed after pre-specified number of events have occurred. All patients randomised to SBRT will be followed minimum 60 months for toxicity. Safety analysis of acute toxicity will take place after median follow up of 6 months. Safety analysis of late toxicity will be analysed after study closure.
Duration of the study:
Three to five years inclusion. 72 months of follow-up after randomization of the last patient.
详细描述
Standard of Care (arm A and B): 3 years of ADT with the addition of abiraterone+prednisolone for two years. If the patient is de novo oligo-metastatic, RT to the prostate +/- pelvic fields is considered as standard treatment.
Study intervention (arm A): MD-SBRT to all PSMA-PET/CT positive metastatic target volume(s) with 30 Gy in 3 fractions or 40 Gy in 5 fractions in addition to SoC. For recurrent patients post prostatectomy with PSMA-PET-positive finding at prostate bed +/- regional lymph nodes (without prior local RT) salvage RT +/-pelvic fields with SIB to the PSMA+ GTV is to be delivered (sum of SBRT-targets maximum 3).
Screening procedure:Inclusion/exclusion criteria evaluation including evaluation of feasibility of SBRT to all positive lesions on PSMA-PET/CT performed within approx. 30 days of randomization.
Study specific procedure: Recording/collecting of baseline data including baseline PROM and pre-ADT testosterone and PSA. Standard treatment with ADT administered at randomization to all study patients. Abiraterone is initiated within 8 weeks of study entry. Start of MD-SBRT within approx. 28 days of randomization to patients in arm A. Additional RT as specified in study intervention started within 90 days. Follow up according to protocol, minimum 60 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed prostate cancer (ICD-O-3 C61)
- •WHO/ECOG performance status 0-1
- •1-3 skeletal or extra pelvic lymph node metastases detected by PSMA-PET/CT in de novo prostate cancer or PSA-relapse after definitive RT or prostatectomy
- •Willing and able to provide informed consent-
排除标准
- •Castration resistant prostate cancer (progression with castrate levels of testosterone)
- •Any treatment known to affect PSA (including ADT) for prostate cancer within 6 months (exception: ADT started due to oligometastatic disease within 2 weeks of study entry)
- •Patient eligible for other treatment (e.g., early docetaxel) than standard treatment described in the protocol as judged by treating physician
- •Life expectancy <3 years by any reason, including concomitant or previous malignancies
- •Previous radiotherapy or surgery that may interfere with the planned treatment (including intra-prostatic recurrence if previous RT to the prostate)
- •> 3 PSMA-PET/CT positive target lesions (excluding the prostate and regional lymph node metastasis in de novo patients or prostate bed and or regional lymph node metastasis in recurrent patients)
- •PSMA-PET verified metastases other than skeletal or lymph nodes
- •Metastases in base of scull and/or calotte
- •Any target lesions not treatable with image guided RT (IGRT) due to overlap with previous RT fields or exceeded dose constraint to OAR(s) as specified in study protocol
研究组 & 干预措施
Standard of Care
ADT+ARPI to all patients and local RT +/- pelvic fields to de novo patients
干预措施: androgen deprivation therapy (Combination Product)
Standard of Care
ADT+ARPI to all patients and local RT +/- pelvic fields to de novo patients
干预措施: Radiotherapy (Radiation)
SBRT+Standard of Care
SBRT to all PSMA+ lesions in addition to SoC and salvage RT to the prostate bed +/- pelvic fields if recurrent post prostatectomy and PSMA-PET+ in the pelvis
干预措施: stereotactic body radiotherapy (Radiation)
SBRT+Standard of Care
SBRT to all PSMA+ lesions in addition to SoC and salvage RT to the prostate bed +/- pelvic fields if recurrent post prostatectomy and PSMA-PET+ in the pelvis
干预措施: androgen deprivation therapy (Combination Product)
SBRT+Standard of Care
SBRT to all PSMA+ lesions in addition to SoC and salvage RT to the prostate bed +/- pelvic fields if recurrent post prostatectomy and PSMA-PET+ in the pelvis
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Failure free survival
时间窗: Throughout the study duration (72 months of follow up for last patient included.)
Time from randomisation to progressive disease. Progression is defined as 2 consecutive rises in blood PSA. PSA will be collected every third month and registered in the electronic case report form.
次要结局
- Outcome prediction(Throughout the study duration (72 months of follow up for last patient included.))
- Overall survival(Throughout the study duration (72 months of follow up for last patient included.))
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.(Until 6 months after randomisation)
- Number of participants with treatment-related serious adverse events as assessed by CTCAE v5.(Throughout the study duration (72 months of follow up for last patient included.))
- Patient reported quality of life assessed by EORTC-QLQ 30(Throughout the study duration (72 months of follow up for last patient included.))
- Castration resistent prostate cancer, CRPC(Throughout the study duration (72 months of follow up for last patient included.))
研究者
Karin Soderkvist
Senior Consultant, PhD
Umeå University