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

NCT ID: NCT05603559

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2026-10-04

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.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.

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 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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

1.1 GBq (30 mCi) of 177Lu-P17-087

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

1.1 GBq (30 mCi) of 177Lu-P17-088

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhaohui Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhaohui Zhu, MD

Role: CONTACT

13611093752@163.com

86-13611093752

Guochang Wang, MD

Role: CONTACT

guochang1007@163.com

86-18516822732

Facility Contacts

Zhaohui Wang, MD

Role: primary

13611093752@163.com

86-13611093752

Guochang Wang, MD

Role: backup

guochang1007@163.com

86-18516822732

References

Li L, Wang J, Wang G, Wang R, Jin W, Zang J, Sui H, Jia C, Jiang Y, Hong H, Zhu L, Alexoff D, Ploessl K, Kung HF, Zhu Z. Comparison of novel PSMA-targeting [177Lu]Lu-P17-087 with its albumin binding derivative [177Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study. Eur J Nucl Med Mol Imaging. 2024 Jul;51(9):2794-2805. doi: 10.1007/s00259-024-06721-x. Epub 2024 Apr 25.

Reference Type: DERIVED

PMID: 38658392 (View on PubMed)

Other Identifiers

PekingUMCH-NM-087/088

Identifier Type: -

Identifier Source: org_study_id