Safety, Dosimetry and Dose-escalation of 177Lu-P17-087/177Lu-P17-088 in Patients With Metastatic Castration-resistant Prostate Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Dosimetry of normal organs and tumors
研究概览
简要总结
This is a pilot study to assess the safety and measure image-based absorbed dose of 177Lu-P17-087/177Lu-P17-088 in patients with metastatic castration-resistant prostate cancer (mCRPC) who will undergo radioliagnd therapy using 177Lu-P17-087/177Lu-P17-088. All patients underwent whole-body 68Ga-PSMA PET/CT for selection and accepted intravenous injection with single dose 1.1 GBq (30 mCi) of 177Lu-P17-087/177Lu-P17-088 within one week, then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours after 177Lu-P17-087/177Lu-P17-088 administration with serial whole body planar and SPECT/CT imaging.Following this initial safety assessment, the study will proceed to a dose-escalation phase designed to further evaluate safety and determine the optimal therapeutic activity. The dose-escalation phase will enroll patients into three sequential cohorts: a 1.11 GBq (30 mCi) dose group, a 2.96 GBq (80 mCi) dose group, and a 4.44 GBq (120 mCi) dose group.
详细描述
Prostate cancer is the most frequent malignant tumor in men worldwide. Prostate-specific membrane antigen (PSMA), is a surface molecule specifically expressed by prostate tumors which was shown to be a valid target for radiotherapy. 177Lu-PSMA-617, a urea-based compound, provide an effective target for the treatment of metastatic castration-resistant prostate cancer. However, a major problem in the therapeutic use of 177Lu-PSMA-617 has been its short half-life and fast rate of clearance. The investigators designed and synthesized a new radiopharmaceutical based on PSMA-11, P16-093. 68Ga-P16-093 showed higher tumor uptake and clear blood clearance than 68Ga-PSMA-617. Then, the investigators shynthesis a new therapeutic radiopharmaceutical based on P16-093, P17-087; and the investigators added a selected albumin binder into P17-088 to synthesis another new radiopharmaceutical, P17-088. This study is designed to evaluate the safety, dosimetry, and preliminary antitumor activity of 177Lu-P17-087/177Lu-P17-088. The trial will include an initial dose-escalation phase to identify the maximum tolerated dose (MTD) or optimal biological dose, which will be followed by a dose-expansion phase to confirm safety and further characterize pharmacokinetics and efficacy, thereby establishing the Recommended Phase II Dose (RP2D) for future development.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •All the patients had progressive metastatic castration-resistant prostate cancer that did not respond to androgen-suppression therapy and/or systemic chemotherapy;
- •Distant metastases with high PSMA expression were confirmed on 68Ga-PSMA PET/CT within one week before the injection of 177Lu-P17-087/177Lu-P17-088.
排除标准
- •Patients were excluded if they had [18F]FDG positive tumors without corresponding PSMA uptake. Patients were also not eligible if they accepted other radionuclide therapies within 6 months or had clinically significant impaired bone marrow, liver, or kidney function with a hemoglobin level of less than 9.0 g/dL, a white blood cell count of less than 2.5×109/L, a platelet count of less than 100×109/L and a serum creatinine > 100 μmol/L.
研究组 & 干预措施
177Lu-P17-087 arm
All patients were intravenous injected with single dose 1.1 GBq (30 mCi) of 177Lu-P17-087 then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours post-injection.
干预措施: 1.1 GBq (30 mCi) of 177Lu-P17-087 (Drug)
177Lu-P17-088 arm
All patients were intravenous injected with single dose 1.1 GBq (30 mCi) of 177Lu-P17-088 then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours post-injection.
干预措施: 1.1 GBq (30 mCi) of 177Lu-P17-088 (Drug)
结局指标
主要结局
Dosimetry of normal organs and tumors
时间窗: Determined using imaging at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours after the first administration of 177Lu-P17-087/088
The semiquantitative dosimetry will be performed based on SPECT/CT acquisitions after the administration of 177Lu-P17-087/177Lu-P17-088. The dose delivered to normal organs and tumors will be recorded.
Hematologic adverse events collection
时间窗: through study completion, an average of 2 weeks
Hematologic status were performed before and every 2 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0.
Hepatic and renal toxic events collection
时间窗: through study completion, an average of 2 weeks
Liver function, and renal function were performed before and 6 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0.
次要结局
- PSA Response(through study completion, an average of 3 weeks)
- PSMA Response(6 weeks after treatment administration.)