Image-Guided Biopsies in Identifying Mechanisms of Resistance in Participants With Metastatic Castration Resistant Prostate Cancer Undergoing Radioligand Therapy

Study Overview
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Brief Summary
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This trial studies image-guided biopsies work in identifying mechanisms of resistance in participants with castration resistant prostate cancer that has spread to other places in the body and who are undergoing radioligand therapy (RLT). Tissue sample collected from a biopsy may help determine why response to RLT varies among patients, and this may help researchers to find better treatments for advanced prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Proportion of metastatic castration resistant prostate cancer (mCRPC) patients with altered signaling pathways after radioligand therapy assessed by phospho-proteomics of biopsy samples. SECONDARY OBJECTIVES: I. Generation of patient derived xenograft (PDX) models to determine if tumor levels of activity for individual adaptive pathways are related to the best prostate specific antigen (PSA) response. II. Sequencing to identify frequently mutated genes such as TP53 and ATM. OUTLINE: Participants undergo image-guided biopsy over 45 minutes prior to first RLT course and 1-2 days after the third RLT course.

Official Title
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Radiologically Guided Biopsies of Metastatic Castration Resistant Prostate Cancer to Identify Adaptive 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

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 Enrolled in Lu-PSMA-617 treatment trial (Institutional Review Board [IRB]# 17-000330) 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 of 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>Participants undergo image-guided biopsy over 45 minutes prior to first RLT course and 1-2 days after the third RLT course. | 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 altered signaling pathways after radioligand therapy (RLT) | No statistical power analysis was performed as this is a pilot study. An unbiased proteomic/phospho-proteomics analysis will be done and it is unknown how many and which parameters will change in response to radioligand therapy. The study will in subsequent studies use the information obtained here to design a more definitive trial. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with gene mutation in regulators of replication stress response according to sequencing | No statistical power analysis was performed as this is a pilot study. An unbiased proteomic/phospho-proteomics analysis will be done and it is unknown how many and which parameters will change in response to radioligand therapy. The study will in subsequent studies use the information obtained here to design a more definitive trial. | Up to 3 years | 
| Generation of xenografts | No statistical power analysis was performed as this is a pilot study. An unbiased proteomic/phospho-proteomics analysis will be done and it is unknown how many and which parameters will change in response to radioligand therapy. The study will in subsequent studies use the information obtained here to design a more definitive trial. | Up to 3 years |