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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer
• Intervention / Treatment: Procedure: Image Guided Biopsy

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 Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diagnostic (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.	Procedure: Image Guided Biopsy; Undergo image guided biopsy; Other Names: Image-Guided Biopsy; Imaging Guided Biopsy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2018
• Primary Completion (ANTICIPATED): June 14, 2021
• Study Completion (ANTICIPATED): June 14, 2022

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (ACTUAL): July 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Carcinoma
• Other Study ID Numbers: 18-000273 (OTHER: UCLA / Jonsson Comprehensive Cancer Center); NCI-2018-01422 (REGISTRY: CTRP (Clinical Trial Reporting Program)); P50CA092131 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No