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

NCT07313241 | Recruiting Phase 2 DMC

• 1 other identifier: 20251220
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• EPIC-26 hormonal summary domain score

  Baseline and regular intervals during 2 year follow up

• EPIC-26 Genitourinary (GU) summary domain score

  Baseline and regular intervals during 2 year follow up

• EPIC-26 Gastrointestinal (GI) summary domain score

  Baseline and regular intervals during 2 year follow up

• CTCAE v5.0 toxicity GU and GI

  Baseline and regular intervals during 2 year follow up

Study Arms (1)

Single Arm: PSA Response Adapted Salvage Radiotherapy

EXPERIMENTAL

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; Radiation: Pelvic nodal Radiotherapy; Drug: Androgen Deprivation Therapy (ADT)

Interventions

Prostate Fossa Radiotherapy RADIATION

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.

Single Arm: PSA Response Adapted Salvage Radiotherapy

Pelvic nodal Radiotherapy RADIATION

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.

Single Arm: PSA Response Adapted Salvage Radiotherapy

Androgen Deprivation Therapy (ADT) DRUG

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.

Single Arm: PSA Response Adapted Salvage Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male only study- Prostate cancer with rising PSA after surgical removal of the prostate and without evidence of disease beyond the prostate bed
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Androgen Antagonists

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Aurelie Garant, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Neufeld, MS

CONTACT

214-645-8525; sarah.hardee@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: December 31, 2025
• Study Start: November 14, 2025
• Primary Completion (Estimated): November 14, 2030
• Study Completion (Estimated): November 14, 2030
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (1)