177Lu-P17-087/177Lu-P17-088 in Patients With Metastatic Castration-resistant Prostate Cancer

Early Phase 1

Completed

• Conditions: Metastatic Castration-resistant Prostate Cancer
• Interventions: Drug: 1.1 GBq (30 mCi) of 177Lu-P17-087; Drug: 1.1 GBq (30 mCi) of 177Lu-P17-088

• Registration Number: NCT05603559
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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.

Detailed Description

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 was designed to investigate the safety, dosimetry and preliminary effects of 177Lu-P17-087/177Lu-P17-088 in patients with metastatic castration-resistant prostate cancer.

Study Timeline

• Study First Submitted: 2022-10-25
• Study First Submitted QC: 2022-10-30
• Study First Posted: 2022-11-02
• Study Start: 2023-01-01
• Primary Completion: 2023-09-05
• Status Verified: 2023-10
• Study Completion: 2023-10-04
• Last Update Submitted: 2023-10-19
• Last Update Posted: 2023-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 9

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
177Lu-P17-087 arm	1.1 GBq (30 mCi) of 177Lu-P17-087	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.
177Lu-P17-088 arm	1.1 GBq (30 mCi) of 177Lu-P17-088	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.

Primary Outcome Measures

Name	Time	Method
Dosimetry of normal organs and tumors	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	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	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.

Secondary Outcome Measures

Name	Time	Method
PSA Response	through study completion, an average of 3 weeks	The serum PSA response was documented semimonthly until 6 weeks after the administration of 177Lu-P17-087/177Lu-P17-088. PSA response was classified as the following: partial response (PR) if PSA decrease ≥50%, progressive disease (PD) if PSA increase ≥ 25% and stable disease (SD) if PSA increase \<25% or PSA decrease \<50%.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China