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

Safety and Dosimetry of 177Lu-P17-087/177Lu-P17-088 in Patients With Metastatic Castration-resistant Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: 1.1 GBq (30 mCi) of 177Lu-P17-087; Drug: 1.1 GBq (30 mCi) of 177Lu-P17-088

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Experimental: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic adverse events collection	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.	through study completion, an average of 2 weeks
Dosimetry of normal organs and tumors	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.	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
Hepatic and renal toxic events collection	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.	through study completion, an average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response	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%.	through study completion, an average of 3 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Zhaohui Zhu, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): September 5, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 30, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PekingUMCH-NM-087/088

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No