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

• ClinicalTrials.gov Identifier: NCT05603559
• Recruitment Status: Completed
• First Posted: November 2, 2022
• Last Update Posted: October 23, 2023
• Sponsor: Peking Union Medical College Hospital
• Information provided by (Responsible Party): Peking Union Medical College Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: 1.1 GBq (30 mCi) of 177Lu-P17-087; Drug: 1.1 GBq (30 mCi) of 177Lu-P17-088	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Safety and Dosimetry of 177Lu-P17-087/177Lu-P17-088 in Patients With Metastatic Castration-resistant Prostate Cancer
• Actual Study Start Date: January 1, 2023
• Actual Primary Completion Date: September 5, 2023
• Actual Study Completion Date: October 4, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Dosimetry of normal organs and tumors [ Time Frame: 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.
2. Hematologic adverse events collection [ Time Frame: 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.
3. Hepatic and renal toxic events collection [ Time Frame: 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 :

1. PSA Response [ Time Frame: 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%.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Peking Union Medical College Hospital

Beijing, Beijing, China, 100730

Sponsors and Collaborators

Peking Union Medical College Hospital

Investigators

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

More Information

• Responsible Party: Peking Union Medical College Hospital
• ClinicalTrials.gov Identifier: NCT05603559
• Other Study ID Numbers: PekingUMCH-NM-087/088
• First Posted: November 2, 2022
• Last Update Posted: October 23, 2023
• Last Verified: October 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases