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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Freedom from failure [Time frame: 2 years from end of radiotherapy]

Secondary outcome measures (4)

• EPIC-26 hormonal summary domain score [Time frame: Baseline and regular intervals during 2 year follow up]
• EPIC-26 Genitourinary (GU) summary domain score [Time frame: Baseline and regular intervals during 2 year follow up]
• EPIC-26 Gastrointestinal (GI) summary domain score [Time frame: Baseline and regular intervals during 2 year follow up]
• CTCAE v5.0 toxicity GU and GI [Time frame: Baseline and regular intervals during 2 year follow up]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UT Southwestern Medical Center-Dallas — Dallas

Identifiers

NCT: NCT07313241 · 20251220

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗