PROstate-specific Membrane Antigen DosImetry-Guided EndoradiotherapY: a Phase 1/2 Study of Personalized PSMA Radiopharmaceutical Therapy (PRODIGY-1)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 500
- 主要终点
- Phase 2: Overall response rate (ORR)
研究概览
简要总结
The goal of this clinical trial is to study a personalized regime of lutetium-177 (177Lu) prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT) in patients with progressive and/or symptomatic, inoperable PSMA-expressing cancers of prostatic or other origins.
The main questions it aims to answer are:
- To establish a dosimetry-based, personalized regime of 177Lu-PSMA
- To report on the efficacy of personalized 177Lu-PSMA
Participants (stratified by risk factors of toxicity) will receive up to 6 cycles of a personalized activity of 177Lu-PSMA based on renal dosimetry. In the phase 1, the prescribed absorbed dose to the kidney will be escalated, to determine the regime that will be administered in the phase 2. The best response within 12 months after the first cycle will be assessed. Salvage treatment of 3 cycles may be offered to responders after re-progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>18 y.o. adults able to provide consent
- •Inoperable or metastatic PSMA-expressing cancer, with significant PSMA expression defined as uptake in at least one lesion that is superior to that of the liver on PSMA positron-emission tomography (PET) within 3 months prior to enrolment
- •Cancer progression documented within 3 months prior to enrolment as per the investigator's assessment, without initiation of another anti-cancer treatment since (excluding palliative radiation therapy to a minority of the tumor burden), unless that anti-cancer treatment was stopped prematurely because of intolerance
- •For participants with a cancer other than mCRPC, a recommendation from a multidisciplinary tumor board (MDT) in favor of PSMA RPT must be obtained
排除标准
- •Platelets < 50 x 106/L
- •Absolute neutrophil count (ANC) < 1.0 x 106/L
- •Eastern Cooperative Oncology Group (ECOG) 4 or prognosis < 3 months, for cancer-related or other serious medical conditions, as per investigator's assessment
- •Known presence of central nervous system metastasis at risk of complication, which cannot be adequately stabilized (e.g. radiotherapy or corticoid prophylaxis), as per investigator's assessment
- •Any condition that would limit the ability to comply with the study protocol, as per investigator's assessment
- •Pregnancy or breastfeeding (e.g. for female participants with non-prostate cancer)
研究组 & 干预措施
Cohort B
Extensive bone metastasis
干预措施: 177Lu-PSMA-I&T - recommended phase 2 regime (Drug)
Cohort D
Renal function impairment
干预措施: 177Lu-PSMA-I&T - recommended phase 2 regime (Drug)
Cohort A
Lower risk of toxicity (no risk factor)
干预措施: 177Lu-PSMA-I&T - escalating renal absorbed dose (Drug)
Cohort A
Lower risk of toxicity (no risk factor)
干预措施: 177Lu-PSMA-I&T - recommended phase 2 regime (Drug)
Cohort B
Extensive bone metastasis
干预措施: 177Lu-PSMA-I&T - escalating renal absorbed dose (Drug)
Cohort C
Decreased bone marrow reserve
干预措施: 177Lu-PSMA-I&T - escalating renal absorbed dose (Drug)
Cohort C
Decreased bone marrow reserve
干预措施: 177Lu-PSMA-I&T - recommended phase 2 regime (Drug)
Cohort D
Renal function impairment
干预措施: 177Lu-PSMA-I&T - escalating renal absorbed dose (Drug)
Cohort E
Higher risk of toxicity (more than one risk factor and others)
干预措施: 177Lu-PSMA-I&T - escalating renal absorbed dose (Drug)
Cohort E
Higher risk of toxicity (more than one risk factor and others)
干预措施: 177Lu-PSMA-I&T - recommended phase 2 regime (Drug)
结局指标
主要结局
Phase 2: Overall response rate (ORR)
时间窗: Up to 12 months
Phase 1: Number of dose-limiting toxicities (DLTs)
时间窗: 12 weeks
Phase 2: Biochemical response rate (PSA50)
时间窗: Up to 12 months
次要结局
- Delayed AEs of particular interest(Up to 5 years)
- Progression-free survival (PFS)(Up to 5 years)
- Phase 1: Overall response rate (ORR)(Up to 12 months)
- Overall survival (OS)(Up to 5 years)
- Frequency and grades of treatment-related adverse events (AEs)(Up to 12 months)
- Quality of life patient-reported outcome measures (PROMs) response rates(Up to 12 months)
- Phase 1: Biochemical response rate (PSA50)(Up to 12 months)