PET/CT Characterization of Treatment Resistance

NCT05647564 | Recruiting DMC

• 5 other identifiers: 2022-0910A534260SMPH/MEDICINE/HEM-ONCNCI-2022-09580Protocol Version 11/15/2025
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Keywords

androgen receptor targeted therapy; imaging

Outcome Measures

Primary Outcomes (5)

• Characterize intrinsic resistance based on FDG and PSMA PET through change in individual lesion update levels.

  Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which less activity is better.

  Baseline to 12 weeks

• Characterize change in intrinsic resistance based on FDG and PSMA PET.

  Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better.

  Baseline to 12 weeks

• Characterize change in intrinsic resistance based on FDG and PSMA PET.

  Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better.

  12 weeks to 36 weeks

• Characterize change in intrinsic resistance based on FDG and PSMA PET.

  Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better.

  Baseline to 36 weeks

• Characterize acquired resistance at the time of progression

  Percentage and absolute changes in individual lesion update levels (ΔiSUVtotal) will be calculated.

  Baseline to 36 weeks

Secondary Outcomes (3)

• Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time to PSA progression

  Baseline to 36 weeks

• Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time to radiographic progression

  Baseline to 36 weeks

• Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time duration on treatment

  Up to 36 weeks

Study Arms (2)

Intrinsic Resistance Cohort (Cohort A)

OTHER

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 .

Diagnostic Test: F-fluorodeoxyglucose positron emission tomography (FDG PET); Diagnostic Test: prostate-specific membrane antigen positron emission tomography (PSMA PET)

Acquired Resistance Cohort (Cohort B)

OTHER

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.

Diagnostic Test: F-fluorodeoxyglucose positron emission tomography (FDG PET); Diagnostic Test: prostate-specific membrane antigen positron emission tomography (PSMA PET)

Interventions

F-fluorodeoxyglucose positron emission tomography (FDG PET) DIAGNOSTIC_TEST

Imaging scan

Acquired Resistance Cohort (Cohort B); Intrinsic Resistance Cohort (Cohort A)

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

Imaging scan

Acquired Resistance Cohort (Cohort B); Intrinsic Resistance Cohort (Cohort A)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men of all races and ethnic groups are eligible for this trial. Women are excluded given that prostate cancer is a male disease.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Glenn Liu, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Robert Jeraj, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 12, 2022
• Study Start: March 6, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)