Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer

Abiraterone/Prednisone + Standard ADT vs Standard ADT for Prostate Cancer Patients With PSMA-Positive Conventional Imaging Negative Pelvic Lymphadenopathy

The advent of PSMA-PET has improved sensitivity and specificity in staging prostate cancer, particularly in intermediate- and high-risk disease. This has created uncertainty in the management of patients with PSMA-positive but conventionally negative pelvic lymphadenopathy (i.e., <1 cm in smallest diameter).

This study evaluates outcomes of enhanced androgen deprivation therapy (ADT) with abiraterone and prednisone compared to standard ADT, both in combination with radiation therapy, in patients with prostate cancer and PSMA-positive but conventionally negative pelvic lymphadenopathy.

A total of 140 eligible participants will be randomized to receive either enhanced ADT with abiraterone and prednisone or standard ADT, both with concurrent radiation therapy. Participants will be followed for 5 years after completion of ADT to assess outcomes.

The primary objective is to determine whether enhanced ADT improves 5-year failure-free survival compared to standard ADT. Secondary objectives include evaluation of toxicity, quality of life, biochemical progression-free survival, cancer-specific survival, overall survival, and metastasis-free survival.

Exploratory objectives include evaluation of tumor growth and regression rates using PSA values and assessment of the relationship between treatment outcomes and blood-based heme oxygenase-1 (HO-1) levels.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Androgen Deprivation Therapy (ADT); Radiation: Radiation Therapy; Drug: Abiraterone; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: IIT OFFICE; Phone Number: 402-559-4596; Email: iitoffice@unmc.edu
• Study Contact Backup: Name: Taylor Johnson, MA; Phone Number: 402-559-4596; Email: taylora.johnson@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
      • Contact: Heather Mittelstedt, RN; Phone Number: 402-559-8287; Email: hmittelstedt@unmc.edu
      • Principal Investigator: Michael Baine, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histopathologically proven diagnosis of local prostate cancer. Biopsies will be confirmed by UNMC pathology review if collected outside our institution.
2. Targetable PSMA-avid pelvic lymph node measuring <1cm in short axis diameter.
3. No prior definitive treatment or intervention received.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 within 14 days prior to registration.
5. Age ≥ 30 years.
6. Patient must be able to provide study-specific informed consent prior to study entry.
7. Patient must be able to swallow medications.

Exclusion Criteria:

1. Evidence of distant metastatic disease outside the pelvic lymph nodes (including osseous pelvic disease).
2. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.
3. Relative or absolute contraindications to radiation therapy as determined by the treating physician. These include, but are not limited to, inflammatory bowel disease, connective tissue disorders (systemic lupus erythematosus, scleroderma, etc.), and genetic disorders that risk increased sensitivity to radiation therapy.

4. Severe, active co-morbidity, defined as follows:

   1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months prior to registration.
   2. Congestive heart failure (NYHA functional capacity class II or greater).
   3. Transmural myocardial infarction within the last 3 months prior to registration.
   4. History of stroke or transient ischemic attack within 3 months prior to registration.
   5. Currently uncontrolled diabetes mellitus.
   6. Ongoing arrhythmias of Grade >2 [National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE), version 5.03]; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
   7. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) in the past month.
   8. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
   9. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
   10. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
   11. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
   12. Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for Disease Control and Prevention definition that is being treated with contraindicated medications, including but not limited to Atazanavir, Saquinavir, Ritonavir, Indinavir, or Nelfinavir. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
   13. Uncontrolled seizures or seizures in the past 3 months. Patients can enroll if their seizures have been well-controlled for >3 months on antiseizure medications.
   14. Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 5 grade 3 or greater within 30 days prior to registration.
   15. History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration.
   16. Total bilirubin ≥1.5X upper limit of normal (ULN) [except for subjects with Gilbert's disease, in which case total bilirubin not to exceed 10X ULN], alanine (ALT) and aspartate (AST) aminotransferase >= 2.5X ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard ADT; Participants receive standard androgen deprivation therapy (ADT) in combination with radiation therapy.	Drug: Androgen Deprivation Therapy (ADT); Standard hormone therapy used for prostate cancer treatment; Radiation: Radiation Therapy; Radiation therapy administered per protocol to the prostate and/or pelvic lymph nodes
Experimental: Abiraterone/Prednisone + Standard ADT; Participants receive Abiraterone/Prednisone in addition to standard androgen deprivation therapy (ADT) in combination with radiation therapy	Drug: Androgen Deprivation Therapy (ADT); Standard hormone therapy used for prostate cancer treatment; Radiation: Radiation Therapy; Radiation therapy administered per protocol to the prostate and/or pelvic lymph nodes; Drug: Abiraterone; Abiraterone administered as part of enhanced androgen deprivation therapy; Drug: Prednisone; Prednisone administered in combination with abiraterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year failure-free survival rate	Determine the impact of enhanced ADT with abiraterone/prednisone versus standard ADT on the 5-year failure-free survival of patients with PSMA-positive conventionally negative pelvic lymphadenopathy (i.e. <1cm in smallest diameter).	From randomization up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity in both arms from 3 months to 2 years post-ADT.	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	From 3 months to 2 years post-ADT
Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (IPSS)	Using IPSS (International Prostate Symptom Score). The quality-of-life measures will be summarized using descriptive statistics at each time point collected as n, mean, SD, median, minimum, and maximum. The IPSS score ranges from 0 to 35, with higher scores indicating worse urinary symptoms.	From 3 months to 2 Years post-ADT
Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (FACT-P)	Using FACT-P (Functional Assessment of Cancer Therapy-Prostate.) The quality of life measures will be summarized using descriptive statistics at each time point collected as n, mean, SD, median, minimum, and maximum. The FACT-P score ranges from0 to 156, with higher scores indicating better quality of life.	From 3 months to 2 Years post-ADT
Evaluate local progression-free survival (i.e., failure-free survival excluding biochemical failure).	Evaluate progression-free survival (i.e., failure-free survival excluding biochemical failure). Progression-free survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Time to local failure is defined as time since randomization to disease progression within the intact prostate. Regional, metastases, and deaths are treated as competing events.	From randomization up to 5 years
Evaluate locoregional progression-free survival (i.e., failure-free survival excluding biochemical failure).	Evaluate progression-free survival (i.e., failure-free survival excluding biochemical failure). Progression-free survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Time to locoregional failure is defined as time since randomization to disease progression within the pelvis and pelvic lymph nodes. Metastases and deaths are treated as competing events.	From randomization up to 5 years
Evaluate 5-year overall survival	Overall survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Overall survival is defined as the time since the date of randomization to the date of death or last follow-up.	From randomization up to 5 years
Evaluate 5-year cancer-specific survival	Cumulative incidence methods will be used to estimate 5-year rates (with 95% CI) of LC, LRC, and DM while accounting for death as a competing event. Cancer-specific survival is defined as time since the date of randomization to the date of death due to cancer diagnosis or treatment or last follow-up. Deaths due to other causes are treated as competing events.	From randomization up to 5 years
Evaluate 5-year metastasis-free survival.	Time to distant metastasis is defined as time since date of randomization to distant metastases in para-aortic lymph nodes and distant organs or last follow-up. Locoregional failures and deaths are treated as competing events.	From randomization up to 5 years

Collaborators and Investigators

• Sponsor: University of Nebraska

Study record dates

Study Major Dates

• Study Start (Estimated): April 3, 2026
• Primary Completion (Estimated): April 3, 2033
• Study Completion (Estimated): April 3, 2033

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; Radiation Therapy; Androgen Deprivation Therapy; Abiraterone; Hormone Therapy; PSMA-PET; Pelvic Lymphadenopathy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Therapeutics; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone; Androgen Antagonists; Radiotherapy; abiraterone
• Other Study ID Numbers: 787-25-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No Plan to Share

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No