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

Not Applicable

Withdrawn

• Conditions: Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer
• Interventions: Procedure: Image Guided Biopsy

• Registration Number: NCT03596710
• Lead Sponsor: Jonsson Comprehensive Cancer Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-06-14
• Status Verified: 2018-07
• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-07-12
• Study First Posted: 2018-07-24
• Last Update Submitted: 2020-07-22
• Last Update Posted: 2020-07-23
• Primary Completion: 2021-06-14
• Study Completion: 2022-06-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (image-guided biopsy)	Image Guided Biopsy	Participants undergo image-guided biopsy over 45 minutes prior to first RLT course and 1-2 days after the third RLT course.

Primary Outcome Measures

Name	Time	Method
Proportion of patients with a successful evaluable biopsy with altered signaling pathways after radioligand therapy (RLT)	Up to 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with gene mutation in regulators of replication stress response according to sequencing	Up to 3 years	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.
Generation of xenografts	Up to 3 years	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.