NRG-GU010: PARALLEL PHASE III RANDOMIZED TRIALS OF GENOMICRISK STRATIFIED UNFAVORABLE INTERMEDIATE RISK PROSTATE CANCER: DE-INTENSIFICATION AND INTENSIFICATION CLINICAL TRIAL EVALUATION (GUIDANCE)

De-Intensification Study:
To determine whether men with National Comprehensive Cancer Network (NCCN)
unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk
(Decipher score < 0.40) treated with RT alone instead of 6 months ADT + RT experience
non-inferior rate of distant metastasis.

Intensification Study:
To determine whether men with NCCN UIR prostate cancer who are in the higher
genomic risk (Decipher score ≥0.40) will have a superior metastasis-free survival through
treatment intensification with darolutamide added to the standard of RT plus 6 months
ADT.

For additional information, please visit: https://classic.clinicaltrials.gov/ct2/show/NCT05050084

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

• Age ≥ 18;
• ECOG Performance Status of 0-2 within 120 days prior to registration;
• Non-castrate testosterone level (>50ng/dL) within 120 days prior to registration;
• Adequate hematologic function within 120 days prior to registration defined as follows:
  • Absolute Neutrophil  1,000 cells/mm3
  • Hemoglobin  8.0 g/dL, independent of transfusion and/or growth factors
  • Platelet count ≥ 100,000 cells/mm3 independent of transfusion and/or growth factors
• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the
  prostate by biopsy, with most recent biopsy (if multiple) within 365 days prior to
  registration;
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following
  bulleted criteria:
  • Has at least one intermediate risk factor (IRF):
  - PSA 10-20 ng/mL
  - Clinical stage T2b-c (DRE and/or imaging) by American Joint Committee on
  Cancer (AJCC) 8th edition
  - Gleason Score 7 (Gleason 3+4 or 4+3 [ISUP Grade Group 2-3])
  • Has ONE or more of the following 'unfavorable' intermediate-risk designators:
  - >1 IRF
  - Gleason 4+3=7 (ISUP Grade Group 3)
  - ≥50% of biopsy cores positive*
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load
  within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility
  for this protocol.
• For patients with a history of hepatitis C virus (HCV) infection must have been treated
  and cured. For patients with HCV infection who are currently on treatment, they are
  eligible if they have an undetectable HCV viral load.

• Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether
  focal or whole-gland (e.g., cryosurgery, HIFU, laser thermal ablation, etc.) for prostate
  cancer.
•  Definitive clinical or radiologic evidence of metastatic disease (M1).
• Prior hematologic or invasive solid tumor malignancy (except non-melanomatous skin
  cancer) unless disease and treatment free for a minimum of 3 years.
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation
  therapy fields.
• Previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin,
  triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide,
  bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed.
•  Active testosterone replacement therapy; 
• Inability to swallow oral pills.
•  High Risk features, which includes any of the following:
  • Gleason 8-10 [ISUP Grade Group 4-5]
  • PSA>20
  • cT3-4 by digital exam OR gross extra-prostatic extension on imaging
  [indeterminate MRI evidence will not count and the patient will be eligible]