Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers (THUNDER): A Two-part Phase 2/3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 493
- 试验地点
- 11
- 主要终点
- Phase 3 Intensification study: Incidence of ppMFS over time. PSMA PET metastatic progression is defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the baseline scan or date of death from any cause.
研究概览
简要总结
Phase 3 Intensification study: To determine improvements in PSMA PET/ CT metastasis-free survival (ppMFS), where ppMFS is defined as the time from randomization to the date of at least 1 new PSMA-PET-positive distant lesion as compared to baseline or date of death from any cause Phase 2 De-intensification study: To determine improvements in Quality of Life indices and effectiveness of up to 96 weeks (24 months) of darolutamide plus SOC RT as an alternative to standard treatment (24 months ADT [LHRHA] plus SOC RT) or standard treatment with ADT plus darolutamide.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histopathology-proven PCa
- •High-risk disease as any of the following factors: PSA > 20 ng/mL or T-stage 3 or 4 or Gleason score 8-10
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
- •Willingness to undergo a PSMA PET/ CT with or without contrast.
- •Willingness to have their primary tumor sequenced for determination of Decipher score
- •Willingness to undergo SOC RT and long-term ADT (treatment with darolutamide and/ or LHRHA)
排除标准
- •Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e., bone scan, CT scan, MRI)
- •PCa with predominant non-adenocarcinoma features (sarcomatoid or spindle or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)
- •Prior pelvic radiotherapy
- •Prior local therapy for PCa
- •Prior systemic therapy for PCa
结局指标
主要结局
Phase 3 Intensification study: Incidence of ppMFS over time. PSMA PET metastatic progression is defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the baseline scan or date of death from any cause.
Phase 3 Intensification study: Incidence of ppMFS over time. PSMA PET metastatic progression is defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the baseline scan or date of death from any cause.
Phase 2 De-intensification study: Health related Quality of Life (HRQL) will be reported by subjects using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. A clinically important point reduction in EPIC subdomain score is defined as follows: sexual (11 points), and hormonal (5 points) as detected at 12 months. EPIC scores will be measured on a yearly basis to monitor late effects.
Phase 2 De-intensification study: Health related Quality of Life (HRQL) will be reported by subjects using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. A clinically important point reduction in EPIC subdomain score is defined as follows: sexual (11 points), and hormonal (5 points) as detected at 12 months. EPIC scores will be measured on a yearly basis to monitor late effects.
次要结局
- OS will be measured from the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored
- Prostate cancer-specific mortality (PCSM) will be measured from the date of randomization to the date of prostate cancer death.
- Biochemical progression-free survival will be measured from the date of randomization to the date event, or death or censored at the last known follow-up date. Events are PSA failure, castrate resistance (EAU Guidelines on Prostate Cancer 2022), receiving salvage therapy, or death from any cause.
- Time to next systemic therapy (NEST) will be measured from date of randomization to time of death, or censored at the last known follow-up date. Events for NEST are receiving any local therapy (surgery, radiotherapy, HIFU, cryotherapy) or systemic therapy for prostate cancer.
- Counts of all AEs by grade will be provided by study (Phase 2 and 3) and treatment arm
- EPIC mean changes in subdomain scores over time will be compared, both for change from baseline and absolute health related quality of life scores.
研究者
Clinical Trials Office
Scientific
Ziekenhuis Aan De Stroom