PSA-response–based androgen deprivation and nodal coverage for early salvage radiotherapy (RANGER)

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

This trial tests whether using early PSA response to decide who gets extra pelvic radiotherapy and a short course of hormone therapy can treat men with rising PSA after prostatectomy while sparing others from unnecessary treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT07313241 on ClinicalTrials.gov

What this trial studies

This Phase II, single-arm study enrolls men with persistent or rising PSA after radical prostatectomy and delivers hypo- or ultra-hypofractionated stereotactic radiotherapy to the prostate fossa using an adaptive radiotherapy platform. PSA response is measured five weeks after treatment start; responders (PSA <0.05 ng/mL or a ≥0.2 ng/mL drop) are observed while non-responders receive sequential pelvic nodal stereotactic radiotherapy plus four months of androgen deprivation therapy. The primary objective is to show non-inferior two-year freedom from progression compared with historical controls where all patients routinely receive pelvic nodal RT and ADT. Secondary endpoints include patient-reported urinary, bowel, and hormonal outcomes and physician-graded GU/GI toxicity, with exploratory evaluation of locoregional and distant failure.

Who should consider this trial

Good fit: Men aged ≥18 who had radical prostatectomy within 10 years with persistent or rising postoperative PSA ≥0.05 ng/mL, ECOG 0–2, no definite regional or distant metastases on required imaging (including PSMA PET when PSA ≥0.2 ng/mL), and able to attend treatment at the study site.

Not a fit: Patients with known regional or distant metastatic disease, prior confirmed nodal involvement (pN1), or those who require immediate systemic therapy are unlikely to benefit from this PSA-adapted salvage approach.

Why it matters

Potential benefit: If successful, this approach could reduce unnecessary pelvic radiation and temporary hormone therapy for men who respond to localized salvage radiotherapy while targeting intensified treatment to those who need it.

How similar studies have performed: While pelvic nodal radiotherapy combined with ADT has shown benefit in prior randomized trials, using early PSA response to selectively escalate with stereotactic nodal RT and short-course ADT is a relatively novel strategy with limited prospective data.

Eligibility criteria

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

Where this trial is running

Dallas, Texas

• UT Southwestern Medical Center-Dallas — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Aurelie Garant, MD — University of Texas Southwestern Medical Center
• Study coordinator: Sarah Neufeld, MS

Conditions Prostate Cancer