for males ages 18 years and up (full criteria)
at Orange, California and other locations
study started
completion around
Principal Investigator
by Steven N. Seyedin



This phase III trial compares stereotactic body radiation therapy (SBRT), (five treatments over two weeks using a higher dose per treatment) to usual radiation therapy (20 to 45 treatments over 4 to 9 weeks) for the treatment of high-risk prostate cancer. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period of time. This trial is evaluating if shorter duration radiation prevents cancer from coming back as well as the usual radiation treatment.

Official Title

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



  1. To compare metastasis-free survival, determined using conventional imaging, between men with high-risk prostate cancer randomized to ultrahypofractionation (stereotactic body radiation therapy [SBRT]) to those randomized to moderate hypofractionation and conventional fractionation.


  1. To compare physician-reported toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 between treatment arms.

II. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported urinary function (assessed by Expanded Prostate Cancer Index Composite [EPIC]-26 urinary domains).

III. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported bowel function (assessed by EPIC-26 bowel domain).

IV. To compare patient-reported fatigue (assessed by Patient Reported Outcomes Measurement Information System [PROMIS]-Fatigue) between treatment arms.

  1. To compare patient-reported treatment burden (assessed by COmprehensive Score for financial Toxicity [COST]) between treatment arms.

VI. To compare failure-free survival between treatment arms. VII. To compare metastasis-free survival based on molecular imaging between treatment arms.

VIII. To compare overall survival between treatment arms.


  1. To compare patient-reported sexual function (assessed by EPIC-26 sexual domain) between treatment arms.

II. To compare patient-reported quality of life (assessed by European Quality of Life Five Dimension Five Level Scale Questionnaire [EQ-5D-5L]) between treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SBRT for a total of 5 treatments over 2 weeks.

ARM II: Patients undergo external beam radiation treatment (EBRT) for 20-45 treatments over 4 to 9 weeks.

Patients are followed up every 6 months for 5 years.


Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Prostatic Neoplasms, External Beam Radiation Therapy, Stereotactic Body Radiation Therapy, SBRT, EBRT


For males ages 18 years and up

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) > 20 ng/mL prior to starting 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 computed tomography (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
  • 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
  • Patients enrolled in NRG-GU009 must be enrolled in NRG-GU013 prior to radiation therapy treatment planning and start of radiation therapy


  • UC Irvine Health/Chao Family Comprehensive Cancer Center accepting new patients
    Orange California 92868 United States
  • Fresno Cancer Center accepting new patients
    Fresno California 93720 United States
  • Kaiser Permanente-Fresno accepting new patients
    Fresno California 93720 United States

Lead Scientist at UC Irvine


accepting new patients
Start Date
Completion Date
NRG Oncology
Phase 3 Prostate Cancer Research Study
Study Type
Expecting 1209 study participants
Last Updated