Phase I/II Dose-Escalation Trial of Combination Fractionated-dose 177Lu-J591 and 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- The Proportion With PSA Decline Following the Dose-Fractionated Combination Therapy by Comparing the Change in PSA Levels After Therapy to the Baseline, Pre-Treatment PSA.
研究概览
简要总结
Phase I dose escalation study with combination of 177Lu-J591 and 177Lu-PSMA-617 using a dose-fractionated regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu-J591 dose for each subject will be 2.7 GBq/m2 (73 mCi/m2) of 177Lu with 20 mg J591 and the cumulative 177Lu-PSMA-617 dose for each subject will vary (depending on the Cohort) from 3.7 GBq (100 mCi) to 18.5 GBq (500 mCi). The 177Lu-PSMA-617 dose will be escalated in up to 6 different dose levels (3+3 dose-escalation study / de-escalation design). For the phase II portion, a minimum number of 14 patients will be enrolled at MTD (including those enrolled at MTD in Phase I) and a maximum of 24.
详细描述
This is an open-label, single-center Phase I dose-escalation study designed to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of combination of 177Lu-J591 and 177Lu-PSMA-617 in a two-week dose-fractionation regimen. 177Lu-J591 will be given at a moderate dose previously demonstrated to be safe x2 infusions two weeks apart. For 177Lu-PSMA-617 the dose escalation will start at 3.7 GBq (100 mCi) and escalate in increments of 1.85 GBq (50 mCi) for each dose to a planned maximum of 9.25 GBq (250 mCi) x2 doses, 2 weeks apart. Should there be unacceptable toxicity at the initial dose level, we will de-escalate to dose level -1 (1.85 GBq / 50 mCi per dose). After the phase I study has established a MTD, the Phase II, single-arm trial will start.
Patients must have documented progressive metastatic CRPC disease based on Prostate Cancer Working Group 3 (PCWG3) criteria in order to be eligible for enrollment. Upon meeting the inclusion and exclusion criteria and signing the informed consent and HIPPA form, subjects will undergo the screening. As part of the screening, subjects will get a single dose of 68Ga-PSMA-HBED-CC and will have a PET/CT. Nuclear Medicine physician(s) will review the PET/CT scans to document PSMA expression at tumor site(s).
Subjects will have Lutetium-177 Planar/SPECT Imaging on Day 8 (±1 day) after the first dose of 177Lu-J591 + 177Lu-PSMA-617. Optimal images will be performed on selected consenting subjects between the initial treatment visit #1 on Day 1 and Day 4 and prior to treatment visit #2 on D15 ±1. Subjects will be closely monitored for AEs (weekly x2 weeks, then every 2 weeks for one month, at 8 and 12 weeks, and then every 4 weeks for next 3 months).
Upon completion of investigational treatment with dose-fractionation regimen of the combination of 177Lu-J591 + 177Lu-PSMA-617, subjects will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT at the end of study visit to document treatment response. Subsequently survival data and additional treatment(s) information will be captured from their routine Standard of care (SOC) visits.
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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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
All Subjects
177Lu-PSMA-617 [1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
177Lu-J591 [1.35 GBq/m2 or 36.5 mCi/m2] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
68Ga-PSMA-HBED-CC [185 ±74 MBq or 5 ±2 mCi] intravenous during screening and at 12 weeks (±1 week) with standard imaging
干预措施: 177Lu-PSMA-617 (Drug)
All Subjects
177Lu-PSMA-617 [1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
177Lu-J591 [1.35 GBq/m2 or 36.5 mCi/m2] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
68Ga-PSMA-HBED-CC [185 ±74 MBq or 5 ±2 mCi] intravenous during screening and at 12 weeks (±1 week) with standard imaging
干预措施: 177Lu-J591 (Drug)
All Subjects
177Lu-PSMA-617 [1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
177Lu-J591 [1.35 GBq/m2 or 36.5 mCi/m2] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration
68Ga-PSMA-HBED-CC [185 ±74 MBq or 5 ±2 mCi] intravenous during screening and at 12 weeks (±1 week) with standard imaging
干预措施: 68Ga-PSMA-HBED-CC (Drug)
结局指标
主要结局
The Proportion With PSA Decline Following the Dose-Fractionated Combination Therapy by Comparing the Change in PSA Levels After Therapy to the Baseline, Pre-Treatment PSA.
时间窗: At baseline and at 2 weeks on therapy
The proportion of patients with PSA decline following treatment with the combination of 177Lu-J591 and 177Lu-PSMA-617 was determined by comparing PSA levels prior to and following radionuclide therapy
Cumulative Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) of Combination Therapy in a 2-Week Dose-Fractionation Regimen
时间窗: Approximately 3 months after enrollment
Cumulative maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of combination therapy was determined by monitoring dose-limiting toxicity and adverse events in the dosing or treatment cohorts
Number of Patients With Dose Limiting Toxicity (DLT) of Combination Therapy in a 2-Week Dose-Fractionation Regimen
时间窗: Approximately 3 months after enrollment
Dose limiting toxicity of combination therapy was determined by monitoring for adverse events following therapy
次要结局
- Number of Subjects With Radiographic Response by RECIST 1.1 With Prostate Cancer Working Group 3 (PCWG3) Modifications(At the efficacy (scan) visit time point (12 weeks))
- Biochemical Progression-Free Survival by PCWG3 Criteria(Through study completion, up to 26 months)
- Rate of Favorable LDH Count(During treatment phase, then every 4 weeks until radiographic progression, assessed up to 6 months)
- Radiographic Progression-Free Survival by PCWG3 Criteria(Through study completion, up to 26 months)
- Rate of Favorable CTC Count as Measured by Cell Search(At the efficacy (scan) visit time point (12 weeks))
- Overall Survival Following Treatment With the Combination of 177Lu-J591 and 177Lu-PSMA-617 in a 2-Week Dose-Fractionation Regimen(Through study completion, up to 26 months)
- Changes in CTC Count as Measured by CellSearch(At the efficacy (scan) visit time point (12 weeks))