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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Radiologically Guided Biopsies of Metastatic Castration Resistant Prostate Cancer to Identify Mechanisms of Resistance in Patients Undergoing 177Lu-PSMA Radioligand Therapy

Conditions
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Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer American Joint Committee on Cancer (AJCC) v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: Image Guided Biopsy


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (image-guided biopsy)<br>Patients undergo an image-guided biopsy at baseline and 2-4 weeks after cycle 2 of 177Lu-PSMA-617 therapy. | Procedure: Image Guided Biopsy<br>* Undergo image-guided biopsy<br>* Other names: Imaging Guided Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |