Recruiting

Treatment Resistance

Sponsor:

University of Wisconsin, Madison

Code:

NCT05647564

Conditions

Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

F-fluorodeoxyglucose positron emission tomography (FDG PET)

prostate-specific membrane antigen positron emission tomography (PSMA PET)

Study Details

Brief summary:

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.

Conditions

Prostate Cancer

Study ID

NCT05647564

Start date

Mar 6, 2023

Status verified date

Feb, 2026

Completion date

Dec 1, 2026

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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, ARSI patients ONLY)
  • Patients must be candidate for a second-generation androgen receptor (AR) inhibitor (e.g. enzalutamide, abiraterone, darolutamide, apalutamide), or Lu177-PSMA radioligand therapy (INTRINSIC RESISTANCE COHORT ONLY)
  • 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, darolutamide, 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) (ACQUIRED RESISTANCE COHORT ONLY)

Exclusion Criteria:

  • Must not have uncontrolled diabetes (fasting blood sugar > 200 mg/dL or inability to safely hold diabetes medication or fast 6 hours prior to FDG PET scan)
  • Prior treatment with second-generation AR inhibitor for prostate cancer in the metastatic disease setting (prior second-generation AR inhibitor in the neoadjuvant or adjuvant setting is permitted unless patient developed progression while on treatment) (INTRINSIC RESISTANCE COHORT, AR-INHIBITOR GROUP ONLY)
  • Pain or clinical symptoms from metastatic prostate cancer requiring opioid analgesics
  • Known neuro-endocrine prostate cancer
  • Prior radioisotope therapy for castration-resistant prostate cancer
  • To avoid the possibility of unintended coercion, vulnerable populations such as incarcerated subjects, subjects unable to provide their own informed consent and non-English speaking patients will not be considered

Study Design

Enrollment

25 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

other: Intrinsic Resistance Cohort (Cohort A)

Participants assigned to Cohort A have advanced prostate cancer and are scheduled to start a second-generation AR-targeted (such as enzalutamide, abiraterone, darolutamide, or apalutamide) or PSMA directed (e.g. Lu177-PSMA) therapies .

other: 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.

Interventions

F-fluorodeoxyglucose positron emission tomography (FDG PET)

Imaging scan

prostate-specific membrane antigen positron emission tomography (PSMA PET)

Imaging scan

Primary outcome measure

  • Characterize intrinsic resistance based on FDG and PSMA PET through change in individual lesion update levels. [ Time Frame: Baseline to 12 weeks ]
  • Characterize change in intrinsic resistance based on FDG and PSMA PET. [ Time Frame: Baseline to 12 weeks ]
  • Characterize change in intrinsic resistance based on FDG and PSMA PET. [ Time Frame: 12 weeks to 36 weeks ]
  • Characterize change in intrinsic resistance based on FDG and PSMA PET. [ Time Frame: Baseline to 36 weeks ]
  • Characterize acquired resistance at the time of progression [ Time Frame: Baseline to 36 weeks ]

Central Contacts and Locations

Central contacts

Cancer Connect

800-622-8922clinicaltrials@cancer.wisc.edu

Locations

University of Wisconsin

Recruiting

Madison, Wisconsin, United States, 53705

Contacts

Cancer Connect

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Christos Kyriakopoulos, MD

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

Sep 1, 2026

Last verified

Feb, 2026

Keywords

  • androgen receptor targeted therapy
  • imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-05. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-09-01.