Active, not recruitingNCT05050084Updated Aug 17, 2026

Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score, The Guidance Trial

A Phase 3 interventional study of Bicalutamide and Buserelin in Prostate Adenocarcinoma, sponsored by NRG Oncology. Active, not recruiting at 576 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-17.

Sponsored by NRG Oncology · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 2,050
Allocation: Randomized
Ages: 18 Years and older
Sex: Male

Study summary

This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Decipher score in this study is used for patient selection and the two variations of treatment to be studied: intensification for higher Decipher score or de-intensification for low Decipher score. Patients with higher Decipher risk score will be assigned to the part of the study that compares the use of 6 months of the usual treatment (hormone therapy and radiation treatment) to the use of darolutamide plus the usual treatment (intensification). The purpose of this section of the study is to determine whether the additional drug can reduce the chance of cancer coming back and spreading in patients with higher Decipher score. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. Alternatively, patients with low Decipher risk score will be assigned to the part of the study that compares the use of radiation treatment alone (de-intensification) to the usual approach (6 months of hormone therapy plus radiation). The purpose of this part of the study is to determine if radiation treatment alone is as effective compared to the usual treatment without affecting the chance of tumor coming back in patients with low Decipher score prostate cancer. Radiation therapy uses high energy to kill tumor cells and reduce the tumor size. Hormone therapy drugs such as darolutamide suppress or block the production or action of male hormones that play role in prostate cancer development. Effect of radiation treatment alone in patients with low Decipher score prostate cancer could be the same as the usual approach in stabilizing prostate cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy.

Read the detailed description

PRIMARY OBJECTIVES:

I. 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 radiation therapy (RT) alone instead of 6 months androgen deprivation therapy (ADT) + RT experience non-inferior rate of distant metastasis. (De-intensification study) II. 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. (Intensification study)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

II. To compare time to prostate specific antigen (PSA) failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

III. To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone).

IV. To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

V. To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions.

VI. To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide).

VII. To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VIII. To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

IX. To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

X. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

XI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

EXPLORATORY OBJECTIVES:

I. To compare changes in cardio-metabolic markers, including body mass index, lipids, blood glucose, complete blood count (CBC), comprehensive metabolic panel (CMP), and hemoglobin (Hgb) A1c, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

II. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

III. To compare cumulative incidence of locoregional failure based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

IV. To compare castrate-resistant prostate cancer (CRPC) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

V. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VI. To compare time to testosterone recovery (defined as a T > 200ng/dL) between the standard of care (RT plus 6 months of ADT) and intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VII. To compare health utilities, as measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VIII. To develop and assess a machine learning/artificial intelligence algorithm for radiotherapy planning and/or quality assurance.

IX. To perform future translational correlative studies using biological data, Decipher results, and clinical outcomes.

OUTLINE:

DE-INTENSIFICATION STUDY: Patients with Decipher score \< 0.40 are randomized to 1 of 2 arms.

ARM I: Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.

INTENSIFICATION STUDY: Patients with Decipher score >= 0.40 are randomized to 1 of 2 arms.

ARM III: Patients receive treatment as in Arm II.

ARM IV: Patients receive RT and ADT as in Arm II. Patients also receive darolutamide orally (PO) twice daily (BID). Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 12, 24, 36, 48 and 60 months.

Conditions studied

Prostate Adenocarcinoma

In context

Lead sponsor

NRG Oncology is the lead sponsor of 72 studies on the registry; 25 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

Inclusion criteria

Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 270 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 (digital rectal examination [DRE] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
  - Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological Pathology (ISUP) Grade Group 2-3])
- Has ONE or more of the following 'unfavorable' intermediate-risk designators:
  - > 1 immature reticulocyte fraction (IRF)
  - Gleason 4+3=7 (ISUP Grade Group 3)
  - >= 50% of biopsy cores positive
    - Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s)
- Absence of high-risk features
Appropriate stage for study entry based on the following diagnostic workup:
- History/physical examination within 120 days prior to registration;
- Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m bone scan or sodium fluoride (NaF) positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities)
- Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =\< 1.0 cm in short axis and/or if biopsy is negative.

Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet pathological criteria based on the latter modalities (e.g. node =\< 10 mm in short axis, negative biopsy), the patient will still be eligible

Age >= 18
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
Absolute neutrophil >= 1,000 cells/mm\^3 (within 120 days prior to registration)
Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
Platelet count >= 100,000 cells/mm\^3 independent of transfusion and/or growth factors (within 120 days prior to registration)
Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
- For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m\^2 will be considered adequate
Total bilirubin: 1.5 =\< institutional upper limit of normal (ULN) (within 120 days prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible)
Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =\< 2.5 x institutional ULN (within 120 days prior to registration)
Human immunodeficiency virus (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 evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
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
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion criteria

Exclusion Criteria:

Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound [HIFU], laser thermal ablation, etc.) for prostate cancer
Definitive clinical or radiologic evidence of metastatic disease (M1)
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is not allowed
Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields
Previous bilateral orchiectomy
Previous hormonal therapy, such as luteinizing hormone-releasing hormone (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
Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped prior to enrollment on the study with at least a 30 day washout period before baseline study PSA measure and registration
Active testosterone replacement therapy; any replacement therapy must be stopped at least 30 days prior to registration
Severe, active co-morbidity defined as follows:
- Current severe or unstable angina;
- New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
- History of any condition that in the opinion of the investigator, would preclude participation in this study
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]

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 2,050 participants (estimated)

Study arms

Experimental
Arm I (RT)
Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.
Radiation: Radiation Therapy
Experimental
Arm II (RT, ADT)
Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.
Drug: Bicalutamide · Drug: Buserelin · Drug: Degarelix · Drug: Flutamide · Drug: Goserelin · Drug: Histrelin · Drug: Leuprolide · Radiation: Radiation Therapy · Drug: Relugolix · Drug: Triptorelin
Experimental
Arm III (RT, ADT)
Patients receive treatment as in Arm II.
Drug: Bicalutamide · Drug: Buserelin · Drug: Degarelix · Drug: Flutamide · Drug: Goserelin · Drug: Histrelin · Drug: Leuprolide · Radiation: Radiation Therapy · Drug: Relugolix · Drug: Triptorelin
Experimental
Arm IV (RT, ADT, darolutamide)
Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Buserelin · Drug: Darolutamide · Drug: Degarelix · Drug: Goserelin · Drug: Histrelin · Drug: Leuprolide · Radiation: Radiation Therapy · Drug: Relugolix · Drug: Triptorelin

Interventions

DrugBicalutamide
Drug
Also known as: Casodex, Cassotide, Cosudex, ICI 176,334, ICI 176334, Utamide
DrugBuserelin
Drug
Also known as: 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig), BSRL, Busereline, Etilamide, HOE 766, HOE-766, HOE766, ICI 123215, ICI-123215, ICI123215, S74 6766, S74-6766, S746766, Tiloryth
DrugDarolutamide
Given PO
Also known as: Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, Nubeqa, ODM 201, ODM-201, ODM201
DrugDegarelix
Drug
Also known as: ASP 3550, ASP-3550, ASP3550, FE 200486, FE-200486, FE200486, Firmagon
DrugFlutamide
Drug
Also known as: 4'-Nitro-3'-trifluoromethylisobutyranilide, Apimid, Cebatrol, Chimax, Cytomid, Drogenil, Euflex, Eulexine, Flucinom, Flucinome, Flugerel, Fluken, Flulem, FLUT, Fluta-Gry, Flutabene, Flutacan, Flutamex, Flutamin, Flutan, Flutaplex, Fugerel, Grisetin, Niftolide, Oncosal, Profamid, Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-, Prostacur, Prostadirex, Prostica, Prostogenat, Sch 13521, Tafenil, Tecnoflut, Testotard
DrugGoserelin
Drug
Also known as: ICI-118630
DrugHistrelin
Drug
DrugLeuprolide
Drug
Also known as: Leuprorelin
RadiationRadiation Therapy
Undergo RT
Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
DrugRelugolix
Drug
Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385, TAK-385, TAK385
DrugTriptorelin
Drug
Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY 25650, AY-25650, AY25650, CL 118532, CL-118,532, CL-118532, CL118532, Detryptoreline

What researchers measure

Primary outcomes

Distant metastasis (DM) (De-intensification study)
Time frame: From randomization to the detection of distant metastasis by conventional imaging, assessed up to 5 years
Metastasis-free survival (MFS) (Intensification study)
MFS will be estimated by the Kaplan-Meier (1958) method and compared between the two treatment arms using a stratified log-rank test (stratified by the randomization stratification factors) at one-sided alpha level of 0.025.
Time frame: From randomization until the occurrence of distant metastasis by conventional imaging or death from any cause, assessed up to 5 years

Secondary outcomes

Overall survival
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test. Cox regression models will also be fit, adjusted for the stratification factors, to estimate hazard ratios, together with 95% confidence intervals.
Time frame: From randomization to death from any cause, assessed up to 5 years
Time to prostate specific antigen (PSA) failure
Defined as PSA \> 2 ng/ml above the nadir post randomization. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Time frame: Up to 5 years
MFS (De-intensification study)
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test. Cox regression models will also be fit, adjusted for the stratification factors, to estimate hazard ratios, together with 95% confidence intervals.
Time frame: From randomization until the occurrence of distant metastasis by conventional imaging or death from any cause, assessed up to 5 years
MFS including positron emission tomography (PET) imaging
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test.
Time frame: From randomization until the occurrence of distant metastasis by conventional and/or molecular imaging or death from any cause, assessed up to 5 years
Locoregional failure (LRF)
Will compare cumulative incidence between arms.
Time frame: From randomization until local or regional recurrence based upon conventional imaging or biopsy, assessed up to 5 years
DM including PET imaging
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Time frame: From randomization to the detection of distant metastasis by conventional and/or molecular imaging, assessed up to 5 years
Prostate cancer-specific mortality
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case death from causes other than prostate cancer as the competing risk.
Time frame: From randomization until death from prostate cancer, assessed up to 5 years
Sexual and hormonal function related quality of life
Measured by the Expanded Prostate Cancer Index Composite-26 (EPIC-26).
Time frame: Up to 5 years
Fatigue
Measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument.
Time frame: Up to 5 years
Cognition
Measured by the Functional Assessment of Chronic illness Therapy-Cognitive (FACT-Cog).
Time frame: Up to 5 years
DM (Intensification study)
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Time frame: From randomization to the detection of distant metastasis by conventional imaging, assessed up to 5 years

Other outcomes

Castrate-resistant prostate cancer (CRPC)
CRPC is defined as PSA increase \> 25% and more than 2 ng/mL above nadir on study in conjunction with a serum testosterone (T) \< 50 ng/mL, confirmed by repeat measurements at least 2 weeks apart. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Time frame: Up to 5 years
Bowel and urinary function related quality of life
Measured EPIC-26. Mixed effect regression models will be fit to compare the changes over time in the domain scores. Covariates will include treatment, time, and treatment-by-time treatment interaction terms.
Time frame: Up to 5 years
Cardio-metabolic markers
Will include body mass index, lipids, blood glucose, complete blood count, comprehensive metabolic panel, and hemoglobin A1c. Mixed effect regression models will be fit to compare the changes over time in the cardio-metabolic markers between treatment groups. Covariates will include treatment, time, and treatment-by-time treatment interaction terms.
Time frame: Up to 5 years
PSA failure-free survival with non-castrate testosterone and no additional therapies
Time frame: Up to 5 years
Locoregional failure based upon either conventional or molecular imaging
Time frame: Up to 5 years
Health utilities
Measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). ). The bootstrap (Efron 1980) will be performed to obtain standard errors, test for significant differences, and generate 95% confidence intervals.
Time frame: Up to 5 years
Time to testosterone recovery
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk. Changes in quality of life measures will be correlated with changes in testosterone levels.
Time frame: From randomization until T > 200 ng/dL, assessed up to 5 years

Study locations

576 sites

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona 85234, United States
Arizona Center for Cancer Care - Gilbert
Gilbert, Arizona 85297, United States
Arizona Center for Cancer Care-Peoria
Peoria, Arizona 85381, United States
Arizona Center for Cancer Care - Phoenix
Phoenix, Arizona 85027, United States
Arizona Center for Cancer Care - Scottsdale
Scottsdale, Arizona 85258, United States
Arizona Center for Cancer Care-Surprise
Surprise, Arizona 85374, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California 95603, United States
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California 93301, United States
Tower Cancer Research Foundation
Beverly Hills, California 90211, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California 95682, United States
City of Hope Corona
Corona, California 92882, United States
City of Hope Comprehensive Cancer Center
Duarte, California 91010, United States
Kaiser Permanente Dublin
Dublin, California 94568, United States
UC San Diego Health System - Encinitas
Encinitas, California 92024, United States
Kaiser Permanente-Fremont
Fremont, California 94538, United States
Washington Hospital
Fremont, California 94538, United States
Kaiser Permanente Fresno Orchard Plaza
Fresno, California 93720, United States
Kaiser Permanente-Fresno
Fresno, California 93720, United States
Marin General Hospital
Greenbrae, California 94904, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612, United States
City of Hope at Irvine Lennar
Irvine, California 92618, United States
UC San Diego Moores Cancer Center
La Jolla, California 92093, United States
City of Hope Antelope Valley
Lancaster, California 93534, United States
Los Angeles General Medical Center
Los Angeles, California 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033, United States
Cedars-Sinai Medical Center
Los Angeles, California 90048, United States
Fremont - Rideout Cancer Center
Marysville, California 95901, United States
Memorial Medical Center
Modesto, California 95355, United States
Kaiser Permanente- Modesto MOB II
Modesto, California 95356, United States
Kaiser Permanente-Modesto
Modesto, California 95356, United States
Providence Queen of The Valley
Napa, California 94558, United States
Kaiser Permanente-Oakland
Oakland, California 94611, United States
Saint Joseph Hospital - Orange
Orange, California 92868, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868, United States
Palo Alto Medical Foundation Health Care
Palo Alto, California 94301, United States
Kaiser Permanente-Roseville
Roseville, California 95661, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California 95661, United States
Kaiser Permanente Downtown Commons
Sacramento, California 95814, United States
Sutter Medical Center Sacramento
Sacramento, California 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817, United States
Kaiser Permanente-South Sacramento
Sacramento, California 95823, United States
California Protons Cancer Therapy Center
San Diego, California 92121, United States
Sharp Memorial Hospital
San Diego, California 92123, United States
Kaiser Permanente-San Francisco
San Francisco, California 94115, United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California 95119, United States
Kaiser Permanente San Leandro
San Leandro, California 94577, United States
Ridley-Tree Cancer Center
Santa Barbara, California 93105, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California 95051, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California 95403, United States
City of Hope South Pasadena
South Pasadena, California 91030, United States
Kaiser Permanente-South San Francisco
South San Francisco, California 94080, United States
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California 94086, United States
Cedars-Sinai Cancer - Tarzana
Tarzana, California 91356, United States
City of Hope South Bay
Torrance, California 90503, United States
Torrance Memorial Physician Network - Cancer Care
Torrance, California 90505, United States
Torrance Memorial Medical Center
Torrance, California 90509, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
Truckee, California 96161, United States
City of Hope Upland
Upland, California 91786, United States
Kaiser Permanente-Vallejo
Vallejo, California 94589, United States
Sutter Solano Medical Center/Cancer Center
Vallejo, California 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California 94596, United States
BASS Medical Group - Lennon
Walnut Creek, California 94598, United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045, United States
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado 80304, United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado 80909, United States
Memorial Hospital North
Colorado Springs, Colorado 80920, United States
Shaw Cancer Center
Edwards, Colorado 81632, United States
Poudre Valley Hospital
Fort Collins, Colorado 80524, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado 80528, United States
Banner North Colorado Medical Center
Greeley, Colorado 80631, United States
UCHealth Greeley Hospital
Greeley, Colorado 80631, United States
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado 80129, United States
Medical Center of the Rockies
Loveland, Colorado 80538, United States
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado 80539, United States
Hartford HealthCare - Saint Vincent's Medical Center
Bridgeport, Connecticut 06606, United States
Danbury Hospital
Danbury, Connecticut 06810, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut 06830, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut 06437, United States
Hartford Hospital
Hartford, Connecticut 06102, United States
Midstate Medical Center
Meriden, Connecticut 06451, United States
The Hospital of Central Connecticut
New Britain, Connecticut 06050, United States
Yale University
New Haven, Connecticut 06520, United States
Norwalk Hospital
Norwalk, Connecticut 06856, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut 06385, United States
Beebe South Coastal Health Campus
Millville, Delaware 19967, United States
Helen F Graham Cancer Center
Newark, Delaware 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware 19713, United States
Beebe Health Campus
Rehoboth Beach, Delaware 19971, United States
George Washington University Medical Center
Washington D.C., District of Columbia 20037, United States
Bay Pines VA Healthcare System
Bay Pines, Florida 33744, United States
Boca Raton Regional Hospital
Boca Raton, Florida 33486, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610, United States
Jupiter Medical Center
Jupiter, Florida 33458, United States
GenesisCare USA - Plantation
Plantation, Florida 33324, United States
Cleveland Clinic-Weston
Weston, Florida 33331, United States
Grady Health System
Atlanta, Georgia 30303, United States

Showing the first 100 of 576 sites across 2 countries.

References and documents

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 17, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05050084
Lead sponsor: NRG Oncology
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Sep 20, 2021
Start date: Dec 6, 2021
Primary completion: Nov 11, 2026 (estimated)
Completion: Nov 11, 2031 (estimated)
Last update: Aug 17, 2026

Study contacts

Neil B Desai

principal investigator · NRG Oncology

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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