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Comparing shorter radiation therapy to standard radiation for high-risk prostate cancer

The Phase III 'High Five Trial' Five Fraction Radiation For High-Risk Prostate Cancer

Phase 3 Interventional NRG Oncology · NCT05946213

This study is testing if a shorter, more intense radiation treatment for high-risk prostate cancer can work just as well as the standard longer treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1209 (estimated)
Ages18 Years and up
SexMale
SponsorNRG Oncology Academic / other
Drugs / interventionsradiation
Locations398 sites (Birmingham, Alabama and 397 other locations)
Trial IDNCT05946213 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of stereotactic body radiation therapy (SBRT), which involves five treatments over two weeks with a higher dose per session, against the conventional radiation therapy that typically requires 20 to 45 treatments over 4 to 9 weeks. The study aims to determine if the shorter duration of SBRT can prevent cancer recurrence as effectively as the standard treatment. It also assesses various secondary outcomes, including treatment toxicity, patient-reported urinary and bowel function, fatigue, and overall survival rates. Participants will be randomized to receive either treatment to compare their outcomes.

Who should consider this trial

Good fit: Ideal candidates include men with high-risk prostate adenocarcinoma who meet specific clinical criteria, such as advanced tumor staging or elevated PSA levels.

Not a fit: Patients with lower-risk prostate cancer or those with contraindications to radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more efficient and less burdensome treatment option for patients with high-risk prostate cancer.

How similar studies have performed: Previous studies have shown promising results with similar hypofractionated radiation approaches, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of prostate cancer
* High-risk disease defined as having at least one or more of the following:

  * cT3a-T3b by digital exam or imaging (American Joint Committee on Cancer \[AJCC\] 8th edition \[Ed.\]) Note: cT4 by imaging or on digital rectal exam is not allowed
  * The patient's prostate specific antigen (PSA) value \> 20 ng/mL prior to starting androgen deprivation therapy (ADT) Note: Patients taking a 5-alpha reductase inhibitor (ex finasteride or dutasteride) are eligible The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors
  * Gleason Score of 8-10
  * Pelvic node positive by conventional imaging with a short axis of at least 1.0 cm
* Prostate gland volume less than 100 cc prior to initiation of ADT as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including MRI or CT scan
* No definitive clinical or radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI); Negative prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is an acceptable substitute
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior radical prostatectomy
* No prior ablative or focal therapy to the prostate (including, but not limited to, transrectal or transurethral high-intensity focused ultrasound \[HIFU\], laser ablation, cryotherapy, irreversible electroporation \[IRE\], and vascular-targeted photodynamic therapy)
* Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone releasing hormone \[LHRH\] agonist and oral anti-androgen) is =\< 185 days prior to registration; Please note: PSA prior to the start of any ADT will be used to define disease
* No contraindication to prostate MRI (required for planning of radiotherapy in both arms)
* Patients enrolled in NRG-GU009 must be enrolled in NRG-GU013 prior to radiation therapy treatment planning and start of radiation therapy

Where this trial is running

Birmingham, Alabama and 397 other locations

+348 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Prostate AdenocarcinomaStage III Prostate Cancer AJCC v8Stage IVA Prostate Cancer AJCC v8
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.