Phase II Trial of PSA Response-based Androgen Deprivation Therapy and Nodal Coverage for Prostate Cancer Early Salvage Radiotherapy (RANGER) ((RANGER))

This Phase II, single arm study evaluates a PSA-response-adapted approach to salvage radiotherapy after radical prostatectomy for prostate cancer. All participants will receive hypo-fractionated stereotactic radiotherapy to the prostate fossa. At 5 weeks, biochemical response will be assessed. responders will proceed to observation, while non responders will receive sequential pelvic nodal radiotherapy and 4 months of androgen deprivation therapy (ADT). The study aims to determine whether this response base approach achieves non inferior 2 year freedom from progression compared with historical outcomes using routine pelvic nodal radiotherapy and ADT in all patients.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Prostate Fossa Radiotherapy; Radiation: Pelvic nodal Radiotherapy; Drug: Androgen Deprivation Therapy (ADT)

Detailed Description

After radical prostatectomy, many men experience biochemical recurrence despite having no visible metastatic disease. Standard salvage radiotherapy is effective but often includes universal use of androgen deprivation therapy and pelvic nodal radiotherapy, which may expose many patients to unnecessary toxicity.

The study evaluates a response adapted strategy using hypo fractionated or ultra hypo fractionated prostate fossa radiotherapy delivered on the Ethos adaptive radiotherapy platform. All participants will undergo 5 fractions of prostate fossa radiotherapy. At 5 weeks from treatment initiation, biochemical response will be defined as PSA <0.05 ng/mL or a 0.2 ng/mL decrease from pre-treatment PSA. Responders will undergo observation. Non responders will receive sequential pelvic nodal stereotactic radiotherapy in 5 fractions and a 4 month course of ADT.

Primary objective is to determine whether PSAA response adapted escalation achieves non inferior 2 year freedom from progression compared with historical control data. Secondary outcomes include patient reported hormonal, urinary, and bowel symptoms (EPIC-26), as well as physician graded gastrointestinal and genitourinary toxicities. Exploratory objectives include evaluating locoregional and distant failure.

This approach may reduce unnecessary toxicity for responders whole allowing early selective intensification for non responders, shortening total treatment duration for all patients.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Neufeld, MS; Phone Number: 214-645-8525; Email: sarah.hardee@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center-Dallas
      • Contact: Sarah Neufeld, MS; Email: Sarah.Neufeld@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men aged ≥18 years with histologically confirmed prostate adenocarcinoma treated with prostatectomy in the localized setting within 10 years, with post-operative PSA (persistent or rising) of ≥0.05ng/mL.
• Radical prostatectomy ≥4 months prior to enrollment without nodal involvement (pN0 or pNx)
• Performance status ECOG 0-2

• No definite evidence of regional or distant metastatic disease by at least pelvic imaging within 90 days of registration. Equivocal findings are allowed at investigator discretion. Imaging is specified as follows:

  • PSA>=0.2ng/mL: positron emission tomography (PET) with FDA-approved advanced imaging agent for prostate cancer (e.g. PSMA) required.
  • PSA <0.2 n/gm: PET with above noted agents OR conventional CT or MRI at investigator discretion.
• All sexually active men must agree to use adequate contraception for the duration of study therapies and a period of 60 days thereafter. Should a female partner of a trial participant become pregnant or suspect she is pregnant while the subject is participating in this study, the patient should inform his treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Prior androgen deprivation therapy (ADT) > 3 months OR anti-androgen therapy (AAT) of > 30 days. For shorter courses of either, at least 30 day "wash out" period is required with confirmation of resolved castration of testosterone to >50ng/mL.
• Ongoing testosterone replacement therapy (TRT) with refusal to discontinue (must be stopped with demonstration of detectable PSA ≥0.05ng/mL and non-castrate testosterone >50ng/mL after 14 days of TRT cessation)
• Prior pelvic radiotherapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• History of bladder neck or urethral stricture requiring procedural intervention.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to actively interfere with the safety or efficacy assessments of this study in the investigator's view.
• Active inflammatory bowel disease requiring recurring systemic or steroid/enema therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm: PSA Response Adapted Salvage Radiotherapy; All participants initially receive prostate fossa radiotherapy (RT) using stereotactic ultra-hypofractionated dosing (32.5 Gy in 5 fractions over 2-4 weeks) delivered via the Ethos™ online adaptive platform. At approximately 5 weeks post-RT initiation, PSA response is assessed: Responders: Patients with PSA <0.05 ng/mL or a decrease of ≥0.2 ng/mL compared to pre-RT PSA will undergo observation without further immediate therapy.; Non-Responders: Patients not meeting response criteria will receive sequential pelvic nodal RT (25 Gy in 5 fractions over ≤4 weeks) plus androgen deprivation therapy (ADT) for 4 months. Pelvic nodal RT begins within 14 days after response assessment. ADT (GnRH agonists/antagonists, e.g., leuprolide, goserelin, degarelix) will be started before or within 14 days of pelvic nodal RT initiation.

Radiation: Prostate Fossa Radiotherapy; Stereotactic ultra hypofractionanted radiotherapy delivered to the prostate fossa using the Ethos online adaptive platform. Total dose of 32.5 Gy administered in 5 fractions over 2-4 weeks.; Radiation: Pelvic nodal Radiotherapy; Sequential pelvic nodal radiotherapy delivered only to PSA non responders. Dose of 25 Gy given in 5 fractions over 4 weeks using the same stereotactic technique as prostate fossa RT.; Drug: Androgen Deprivation Therapy (ADT); GnRH agonist or antagonist (leuprolide, goserelin, degarelix) administered as per institutional standard. Therapy duration is 4 months, starting before or within 14 days of pelvic nodal RT initiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from failure	first occurrence of rise of PSA of 2 ng/dL above post-salvage RT nadir, clinical progression (local/regional/distant) or death due to any cause.	2 years from end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EPIC-26 hormonal summary domain score	Patient reported hormonal symptom severity measure by the EPIC-26 questionnaire	Baseline and regular intervals during 2 year follow up
EPIC-26 Genitourinary (GU) summary domain score	Patient reported genitourinary symptom severity measure by EPIC-26	Baseline and regular intervals during 2 year follow up
EPIC-26 Gastrointestinal (GI) summary domain score	Patient reported gastrointestinal severity measured by EPIC-26	Baseline and regular intervals during 2 year follow up
CTCAE v5.0 toxicity GU and GI	GI and GU adverse events will be assessed and graded according to the National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE), version 5.0.	Baseline and regular intervals during 2 year follow up

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Aurelie Garant, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2025
• Primary Completion (Estimated): November 14, 2030
• Study Completion (Estimated): November 14, 2030

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• 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; Pharmacologic Actions; Chemical Actions and Uses; Androgen Antagonists
• Other Study ID Numbers: 20251220

Drug and device information, study documents

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