Title
PET/CT Characterization of Treatment Resistance

Description
This study will use different types of medical imaging to assess how lesions from advanced prostate cancer become resistant to second-generation AR-targeted therapy, and how the different types of imaging compare in that assessment. Participants in this study have advanced prostate cancer and are either scheduled to start a second-generation androgen receptor (AR) targeted therapy (such as enzalutamide, abiraterone, or apalutamide) or are already being treated with one. Participants can expect to be in the study for at least 9 months, and up to 2 years.
There are two groups, or cohorts, in this study. Participants are assigned to Cohort A if they have advanced prostate cancer and are scheduled to start a second-generation AR-targeted therapy (such as enzalutamide, abiraterone, or apalutamide). Participants are assigned to Cohort B if they have advanced prostate cancer, are already on a second-generation AR-targeted therapy, and have shown an increase in their PSA (prostate-specific antigen) levels.

There are two medical imaging scans that will be done for research purposes in this study. One is called 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and the other is prostate-specific membrane antigen positron emission tomography (PSMA PET). These scans are done simultaneously with computed tomography (CT) scanning. Participants will be scheduled to have 6 scans, 3 FDG PET/CT scans and 3 PSMA PET/CT scans.

Objective
Intrinsic Resistance Cohort
Primary Objective:
- To characterize intrinsic resistance based on FDG PET/CT
- To characterize intrinsic resistance based on PSMA PET/CT
Secondary Objectives:
- To correlate amount of resistance on FDG and PSMA PET/CT to time to PSA progression (PCWG1)
- To correlate amount of resistance on FDG and PSMA PET/CT to time to radiographic progression (PCWG2)
- To correlate amount of resistance on FDG and PSMA PET/CT to time to No Longer Clinical Benefit (PCWG3)

Acquired Resistance Cohort
Primary Objectives:
- To characterize acquired resistance based on FDG PET/CT
- To characterize acquired resistance based on PSMA PET/CT
Secondary Objectives:
- To correlate amount of resistance on FDG and PSMA PET/CT to time to radiographic progression (PCWG2)
- To correlate amount of resistance on FDG and PSMA PET/CT to duration on treatment (PCWG3)

Treatment Intrinsic Resistance Cohort (Cohort A)
Participants assigned to Cohort A have advanced prostate cancer and are scheduled to start a second-generation AR-targeted therapy (such as enzalutamide, abiraterone, or apalutamide).

Acquired Resistance Cohort (Cohort B)
Participants are assigned to Cohort B if they have advanced prostate cancer, are already on a second-generation AR-targeted therapy, and have shown an increase in their PSA (prostate-specific antigen) levels.

Key Eligibility Inclusion Criteria:

Histologically proven adenocarcinoma of the prostate.

At least 1 radiographic metastases as seen on conventional CT imaging or bone scan

Progressive prostate cancer as evident by at least two separate increase in PSA over nadir, and absolute PSA value at least 2 ng/ml (INTRINSIC RESISTANCE COHORT ONLY)

Patients must be candidate for a second-generation androgen receptor (AR) inhibitor (e.g. enzalutamide, abiraterone, apalutamide)

Men of age >18 years.

Patients must be able to comply with all study procedures, including having both the ability and willingness to lie flat for >/= 30 minutes during imaging

Patients must be informed of the exploratory nature of the study and its potential risks, and must sign IRB- approved consent form indicating such understanding.

Life-expectancy at least 12 months

Patients currently receiving a second-generation androgen receptor (AR) inhibitor (e.g. enzalutamide, abiraterone, apalutamide) and must have had 1) PSA decline on treatment and 2) now have PSA increase over nadir while still on treatment (patients must be registered within 12 weeks of first documented PSA increase) (ACQURED RESISTANCE COHORT ONLY)

Applicable Disease Sites
Prostate

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital