Image-Guided Biopsies to Identify Mechanisms of Resistance in Patients With Metastatic Castration Resistant Prostate Cancer Treated With 177Lu-PSMA Radioligand Therapy

Phase 1

Recruiting

• Conditions: Stage IVA Prostate Cancer AJCC v8; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer American Joint Committee on Cancer (AJCC) v8; Castration-Resistant Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8
• Interventions: Procedure: Image Guided Biopsy

• Registration Number: NCT05398302
• Lead Sponsor: Jonsson Comprehensive Cancer Center

Brief Summary

This clinical trial studies mechanisms of resistance to 177-lutetium prostate specific membrane antigen (177Lu-PSMA) radioligand therapy using image-guided biopsies in patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). Diagnostic procedures, such as image guided biopsies, may help in learning how well 177Lu-PSMA works to kill tumor cells and allow doctors to plan better treatment.

Detailed Description

PRIMARY OBJECTIVE:

I. Proportion of metastatic castration resistant prostate cancer (mCRPC) patients with molecular and cellular alterations in tumor, immune and stromal cells after radioligand therapy assessed by histopathology/immunohistochemistry, ribonucleic acid (RNA)-sequencing and proteomic/phospho-proteomic analyses of biopsy samples.

SECONDARY OBJECTIVE:

I. Sequencing to identify frequently mutated genes.

OUTLINE:

Patients undergo an image-guided biopsy at baseline and 2-4 weeks after cycle 2 of 177Lu-PSMA-617 therapy.

Study Timeline

• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-26
• Study First Posted: 2022-05-31
• Study Start: 2024-04-26
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-13
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

• Volunteer patient
• Histologically confirmed prostate cancer
• Eligible for 177Lu-PSMA-617 under expanded access protocol (IRB# 21-5010) or as part of an approved trial
• Based on positron emission tomography (PET)/computed tomography (CT) images: Evidence of lymph node or soft tissue metastatic disease amenable to image-guided biopsy
• Platelets > 75,000/ul within 14 days prior to biopsy
• Prothrombin time (PT) or International normalized ratio (INR) and a partial thromboplastin time (PTT) < 1.5 times the institutional upper limit normal (ULN) within 14 days prior to biopsy
• Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation for one week prior to the biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is agreement regarding the procedure between the treating physician, the interventional radiologist and the principal investigator (PI)

Exclusion Criteria

• Patients with significant congenital or acquired bleeding disorders (e.g. von Wildebrand's disease, acquired bleeding factor inhibitors) are not eligible

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (image-guided biopsy)	Image Guided Biopsy	Patients undergo an image-guided biopsy at baseline and 2-4 weeks after cycle 2 of 177Lu-PSMA-617 therapy.

Primary Outcome Measures

Name	Time	Method
Proportion of patients with a successful evaluable biopsy with molecular and cellular alterations after radioligand therapy (RLT)	At the end of cycle 2 before the initiation of cycle 3 of RLT (cycle is six weeks)

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with gene mutations that might confer resistance to RLT	At the end of cycle 2 before the initiation of cycle 3 of RLT (cycle is six weeks)

Trial Locations

Locations (1)

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States