Two Studies for Patients With High 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 High Gene Risk Score, The PREDICT-RT Trial

Prostate Adenocarcinoma Clinical Trial

Official title:

Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04513717
• Other study ID #: NRG-GU009
• Secondary ID: NCI-2020-04705NR
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2020
• Est. completion date: December 31, 2033

Study information

• Verified date: February 2024
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.

Description:

PRIMARY OBJECTIVES:

I. To determine whether men with National Comprehensive Cancer Network (NCCN) high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (=< 0.85) can be treated with 12 months androgen deprivation therapy (ADT) plus radiation therapy (RT) instead of 24 months ADT+RT and experience non-inferior metastasis-free survival. (De-intensification study) II. To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (> 0.85) or have node-positive disease by conventional imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide added to the standard of RT plus 24 month ADT. (Intensification study)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To compare time to prostate specific antigen (PSA) failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) III. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) IV. To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) V. To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VI. To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VII. To compare time to testosterone recovery (defined as a T > 200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VIII. To compare adverse events, both clinician-reported using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and patient-reported using Patient Reported Outcome (PRO)-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies)

EXPLORATORY OBJECTIVES:

I. To compare changes in cardio-metabolic markers, including body mass index, and waist circumference, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To determine a machine learning/artificial intelligence algorithm for radiotherapy quality assurance. (De-intensification and Intensification studies) III. To perform future translational correlative studies using biological and imaging data. (De-intensification and intensification studies) IV. Impact of PET use in high-risk prostate cancer

PATIENT-REPORTED OUTCOMES OBJECTIVES:

PRIMARY OBJECTIVES:

I. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

SECONDARY OBJECTIVES:

I. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

EXPLORATORY OBJECTIVES:

I. 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 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. 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 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) III. To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) IV. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) 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 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) VI. 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 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

OUTLINE: Patients are randomized to 1 of 4 arms.

DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.85):

ARM I: Patients undergo radiation therapy (RT) over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity.

INTENSIFICATION STUDY (DECIPHER SCORE > 0.85 OR NODE POSITIVE):

ARM III: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide orally (PO) once daily (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2478
• Est. completion date: December 31, 2033
• Est. primary completion date: December 31, 2033
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION

• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration

• High-risk disease defined as having at least one or more of the following:

• PSA > 20 ng/mL prior to starting ADT Note: Patients receiving a 5-alpha reductase inhibitor (ex. finasteride) at the time of enrollment are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors and the medication should be discontinued prior to randomization but a washout period is not required.

• cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.])

• Gleason score of 8-10

• Node positive by conventional imaging with a short axis of at least 1.0 cm

• Appropriate stage for study entry based on the following diagnostic workup:

• History/physical examination within 120 days prior to registration;

• Bone imaging within 120 days prior to registration;

• Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative NaF PET/CT or negative Axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or NaF PET will still be eligible

• CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only

• Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by =10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure = 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study

• Age = 18

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration

• Hemoglobin = 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)

• Platelet count = -100 x 10^3/uL 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 Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility

• Either a CrCl = 30 ml/min or calculated glomerular filtration rate (GFR) = 30 will make a patient eligible

• Total bilirubin =< 1.5 x 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 and if direct bilirubin is = 1.5 x ULN, subject is eligible

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = 2.5 x institutional ULN (within 120 days prior to registration)

• Serum albumin = 3.0 g/dL (within 120 days prior to registration)

• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count = 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with apalutamide

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

• PRIOR TO STEP 2 RANDOMIZATION

• Confirmation of Decipher score

• 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 within 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol

• For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization

Exclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION:

• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI)

• Prior systemic chemotherapy within = 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration

• Prior radical prostatectomy

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible

• History of any of the following:

• Seizure disorder

• 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

• Evidence of any of the following at registration:

• Active uncontrolled infection requiring IV antibiotics

• Baseline severe hepatic impairment (Child Pugh Class C)

• Inability to swallow oral pills

• Any current condition that in the opinion of the investigator, would preclude participation in this study

• 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 = 60 days prior to registration; Please note: baseline PSA must be obtained prior to the start of any ADT

• PRIOR TO STEP 2 RANDOMIZATION:

• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration

• For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] = 160 mmHg or diastolic BP = 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment

Related Conditions & MeSH terms

• Metastatic Malignant Neoplasm in the Bone
• Neoplasms
• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Stage III Prostate Cancer AJCC v8
• Stage IIIA Prostate Cancer AJCC v8
• Stage IIIB Prostate Cancer AJCC v8
• Stage IIIC Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8

Intervention

Drug:
• Apalutamide
Nonsteroidal Antiandrogen
• Bicalutamide
Antiandrogen
• Buserelin
Luteinizing hormone-releasing hormone (LHRH) agonist
• Degarelix
Gonadotropin-releasing hormone (GnRH) antagonist
• Flutamide
Antiandrogen
• Goserelin
Gonadotropin-releasing hormone (GnRH) agonist
• Histrelin
Gonadotropin-releasing hormone (GnRH) agonist
• Leuprolide
Gonadotropin-releasing hormone (GnRH) agonist

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Radiation:
• Radiation Therapy
Undergo radiation therapy

Drug:
• Triptorelin
Gonadotropin-releasing hormone (GnRH) agonist

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Lovelace Radiation Oncology	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Inova Alexandria Hospital	Alexandria	Virginia
United States	Saint Luke's Cancer Center - Allentown	Allentown	Pennsylvania
United States	UPMC Altoona	Altoona	Pennsylvania
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory Proton Therapy Center	Atlanta	Georgia
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Maryland Proton Treatment Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Advocate Good Shepherd Hospital	Barrington	Illinois
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	Houston Methodist San Jacinto Hospital	Baytown	Texas
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Suburban Hospital	Bethesda	Maryland
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Hartford HealthCare - Saint Vincent's Medical Center	Bridgeport	Connecticut
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	University of Michigan - Brighton Center for Specialty Care	Brighton	Michigan
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sands Cancer Center	Canandaigua	New York
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Duke Cancer Institute Cary	Cary	North Carolina
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Saint Luke's Hospital	Cedar Rapids	Iowa
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Chambersburg Hospital	Chambersburg	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Atrium Health University City/LCI-University	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Ascension Calumet Hospital	Chilton	Wisconsin
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Michigan Healthcare Professionals Clarkston	Clarkston	Michigan
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	Noyes Memorial Hospital/Myers Cancer Center	Dansville	New York
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina
United States	Saint Luke's Hospital-Anderson Campus	Easton	Pennsylvania
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Shaw Cancer Center	Edwards	Colorado
United States	Crossroads Cancer Center	Effingham	Illinois
United States	AtlantiCare Surgery Center	Egg Harbor Township	New Jersey
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Exeter Hospital	Exeter	New Hampshire
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Inova Fair Oaks Hospital	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Farmington Health Center	Farmington	Utah
United States	Michigan Healthcare Professionals Farmington	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	MUSC Health Florence Medical Center	Florence	South Carolina
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	Northwell Health Physicians Partners Radiation Medicine at Queens	Forest Hills	New York
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Washington Hospital	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Arizona Breast Cancer Specialists-Gilbert	Gilbert	Arizona
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
United States	Crozer Regional Cancer Center at Brinton Lake	Glen Mills	Pennsylvania
United States	Glens Falls Hospital	Glens Falls	New York
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Marin General Hospital	Greenbrae	California
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Smilow Cancer Hospital Care Center at Greenwich	Greenwich	Connecticut
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Methodist West Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Methodist Willowbrook Hospital	Houston	Texas
United States	Novant Health Cancer Institute - Huntersville	Huntersville	North Carolina
United States	IRMC Cancer Center	Indiana	Pennsylvania
United States	City of Hope at Irvine Lennar	Irvine	California
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Freeman Health System	Joplin	Missouri
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	GenesisCare USA - Lakewood Ranch	Lakewood Ranch	Florida
United States	City of Hope Antelope Valley	Lancaster	California
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Sparrow Hospital	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Healthcare Professionals Macomb	Macomb	Michigan
United States	Michigan Healthcare Professionals Madison Heights	Madison Heights	Michigan
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Thompson Oncology Group-Maryville	Maryville	Tennessee
United States	Novant Health Cancer Institute - Matthews	Matthews	North Carolina
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Yolanda G Barco Oncology Institute	Meadville	Pennsylvania
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Midstate Medical Center	Meriden	Connecticut
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	Miami Cancer Institute	Miami	Florida
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Zablocki Veterans Administration Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	UPMC Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	Monticello Cancer Center	Monticello	Minnesota
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Novant Health Cancer Institute - Mooresville	Mooresville	North Carolina
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Intermountain Medical Center	Murray	Utah
United States	Carolina Regional Cancer Center	Myrtle Beach	South Carolina
United States	Providence Queen of The Valley	Napa	California
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Houston Methodist Saint John Hospital	Nassau Bay	Texas
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Drexel Town Square Health Center	Oak Creek	Wisconsin
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Thompson Oncology Group-Oak Ridge	Oak Ridge	Tennessee
United States	Kaiser Permanente-Oakland	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	GenesisCare USA - Plantation	Plantation	Florida
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Luke's Hospital - Upper Bucks Campus	Quakertown	Pennsylvania
United States	Saint Luke's Hospital-Quakertown Campus	Quakertown	Pennsylvania
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	UNC Rex Cancer Center of Wakefield	Raleigh	North Carolina
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Queens Cancer Center	Rego Park	New York
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Bon Secours Cancer Institute at Reynolds Crossing	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Hospital	Ridgewood	New Jersey
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Riverton Hospital	Riverton	Utah
United States	Oncology and Hematology Associates of Southwest Virginia	Roanoke	Virginia
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	University of Utah Sugarhouse Health Center	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Stanford Cancer Center South Bay	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	UCSF Cancer Center - San Mateo	San Mateo	California
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Arizona Breast Cancer Specialists-Scottsdale	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Vincent Hospital Cancer Center at Sheboygan	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Memorial Hospital East	Shiloh	Illinois
United States	Phelps Memorial Hospital Center	Sleepy Hollow	New York
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	City of Hope South Pasadena	South Pasadena	California
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Dana-Farber/Brigham and Women's Cancer Center at South Shore	South Weymouth	Massachusetts
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Smilow Cancer Hospital Care Center at Long Ridge	Stamford	Connecticut
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Saint Luke's Hospital - Monroe Campus	Stroudsburg	Pennsylvania
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Novant Cancer Institute Radiation Oncology - Supply	Supply	North Carolina
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Tampa General Hospital	Tampa	Florida
United States	Cedars-Sinai Cancer - Tarzana	Tarzana	California
United States	Houston Methodist The Woodlands Hospital	The Woodlands	Texas
United States	Community Medical Center	Toms River	New Jersey
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	City of Hope South Bay	Torrance	California
United States	Torrance Memorial Medical Center	Torrance	California
United States	Torrance Memorial Physician Network - Cancer Care	Torrance	California
United States	Munson Medical Center	Traverse City	Michigan
United States	GenesisCare USA - Troy	Troy	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	UPMC Cancer Center-Uniontown	Uniontown	Pennsylvania
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Westchester Medical Center	Valhalla	New York
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	UPMC Cancer Center-Washington	Washington	Pennsylvania
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Wilmot Cancer Institute at Webster	Webster	New York
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Reading Hospital	West Reading	Pennsylvania
United States	Smilow Cancer Hospital Care Center - Westerly	Westerly	Rhode Island
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Divine Providence Hospital	Williamsport	Pennsylvania
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Novant Health Cancer Institute Radiation Oncology - Wilmington	Wilmington	North Carolina
United States	Novant Health New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	University of Michigan Health - West	Wyoming	Michigan
United States	UPMC Memorial	York	Pennsylvania
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cardio-metabolic markers including body mass index and waist circumference		Up to 13 years
Other	Machine learning/artificial intelligence algorithm		Up to 13 years
Other	Bowel and urinary quality of life (De-intensification study)	Measured by EPIC-26 bowel and urinary domains.	Up to 13 years
Other	Cognition (De-intensification study)	Measured by the Functional Assessment of Chronic Illness Therapy-Cognition (FACIT-Cog) perceived cognitive abilities subscale.	Up to 13 years
Other	Sexual, hormonal, bowel, and urinary quality of life (Intensification study)	Measured by Expanded Prostate Cancer Index Composite-26.	Up to 13 years
Other	Cognition (Intensification study)	Measured by the FACIT-Cog perceived cognitive abilities subscale.	Up to 13 years
Primary	Metastasis-free survival (MFS)	Assessed based on conventional imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958).	From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years
Secondary	MFS	Assessed based on standard or molecular, if available, imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958)	From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years
Secondary	Overall survival	Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).	From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 13 years
Secondary	Prostate cancer specific mortality (PCSM)		From the date of randomization to the date of prostate cancer death, assessed up to 13 years
Secondary	Prostate specific antigen (PSA) failure-free survival with non-castrate testosterone and no additional therapies	PSA failure-free survival will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).	From the date of randomization to the date event, or death or censored at the last known follow-up date, assessed up to 13 years
Secondary	Time to testosterone recovery	Defined as testosterone that is non-castrate.	Up to 13 years
Secondary	Time to PSA failure or salvage therapy		Up to 13 years
Secondary	Testosterone levels at the time of PSA failure and metastases		Up to 13 years
Secondary	Incidence of adverse events	Measured by the Common Terminology Criteria for Adverse Events (CTCAE ) version (v) 5.0 and Patient Reported Outcomes (PRO)-CTCAE.	Up to 13 years