BIOMARKER TRIAL of APALUTAMIDE and RADIATION for RECURRENT PROSTATE CANCER

PSA Progression Clinical Trial

— BALANCE  

Official title:

A Phase II, Double-Blinded, Placebo Controlled Randomized Trial of Salvage Radiotherapy With or Without Enhanced Anti-androgen Therapy With Apalutamide in Recurrent Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03371719
• Other study ID #: NRG-GU006
• Secondary ID: NCI-2017-01268NR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 27, 2018
• Est. completion date: October 31, 2028

Study information

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

Clinical Trial Summary

This phase II trial studies how well radiation therapy with or without apalutamide works in treating patients with stage III-IV prostate cancer. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgen can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may lessen the amount of androgen made by the body. Giving radiation therapy and apalutamide may work better at treating prostate cancer than radiation alone.

Description:

PRIMARY OBJECTIVES:

I. To determine whether, in men with post-prostatectomy PSA recurrences, salvage radiation (SRT) with enhanced anti-androgen therapy with apalutamide will improve biochemical progression-free survival (bPFS) compared to SRT alone.

SECONDARY OBJECTIVES:

I. To assess whether molecular stratification by the PAM50 gene expression clustering will identify subsets of prostate cancer (luminal A or basal, luminal B) which derive the greatest benefit from anti-androgen therapy.

II. To assess overall survival. III. To assess cancer-specific mortality. IV. To assess metastasis-free survival. V. To assess distant metastasis. VI. To assess local-regional progression. VII. To assess PSA nadir during first year of treatment and prior to initiation of any hormonal salvage therapy.

VIII. To assess initiation of salvage hormonal therapy. IX. To assess PSA with a non-castrate testosterone at 1 and 3 years post randomization: PSA < 0.1 ng/ml and testosterone >= 50 ng/dl.

X. To assess acute and late physician-reported morbidity (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5) after SRT +/- apalutamide.

XI. To assess acute and late patient-reported morbidity (per the patient reported outcomes [PRO]-CTCAE) after SRT +/- apalutamide.

XII. To assess testosterone levels at 3, 6, 9, 12, and 36 months post randomization.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo external beam radiation therapy on Day 1 for 7.5 weeks. Beginning on Day 1 of radiation therapy, patients receive placebo orally (PO) once daily (QD) on days 1-30. Treatment repeats every 30 days for up to 6 courses (6 months) in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients undergo external beam radiation therapy on Day 1 for 7.5 weeks. Beginning on Day 1 of radiation therapy, patients receive apalutamide PO QD on Days 1-30. Treatment repeats every 30 days for up to 6 courses (6 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and then yearly thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 311
• Est. completion date: October 31, 2028
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically (histologically) proven diagnosis of prostate adenocarcinoma; prostatectomy must have been performed within 10 years prior to Step 1 registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted

• Post-prostatectomy patients with a detectable serum PSA (= 0.1, but = 1.0 ng/mL) at study entry (within 90 days of Step 1 registration) and at least one of the following:

• Gleason score 7-10 (International Society of Urological Pathology [ISUP] grade group 2 to 5)

• ISUP grade group:

• Grade Group 1: Gleason score = 6,

• Grade Group 2: Gleason score 3 + 4 = 7,

• Grade Group 3: Gleason score 4 + 3 = 7,

• Grade Group 4: Gleason score 8,

• Grade Group 5: Gleason scores 9 and 10

• >= T3a disease

• Persistent elevation of PSA after prostatectomy measured within 90 days after surgery (PSA never became undetectable) of > 0.04 but < 0.2 ng/mL (PSA nadir)

• pN0 or pNx

• History/physical examination within 90 days prior to Step 1 registration

• Karnofsky performance status of 70-100 within 90 days prior to Step 1 registration

• Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on Decipher GRID platform; Note: if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation

• Prior androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to Step 1 registration and given for = 90 days duration

• For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date

• Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility

• Hemoglobin = 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to Step 1 registration

• Platelet count = 100,000 x 10^9/uL independent of transfusion and/or growth factors within 90 days prior to step 1 registration

• Serum albumin = 3.0 g/dL within 90 days prior to Step 1 registration

• Glomerular filtration rate (GFR) = 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to Step 1 registration

• Serum total bilirubin = 1.5 x upper limit of normal (ULN) (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) within 90 days prior to Step 1 registration

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN within 90 days prior to Step 1 registration

• Testosterone > 50 ng/dL within 90 days prior to Step 1 registration

• Concomitant medications known to lower the seizure threshold discontinued or substituted at least 4 weeks (30 days) prior to Step 1 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

• The patient must agree not to donate sperm during the study treatment and for 3 months after receiving the last dose of study drug

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

Exclusion Criteria:

• Definitive clinical, radiologic, or pathologic evidence of metastatic disease (M1) or lymph node involvement (N1)

• Prior invasive malignancy (except non-melanomatous skin cancer, carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years

• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable

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

• History of any of the following:

• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to Step 1 registration)

• History of documented inflammatory bowel disease

• Transmural myocardial infarction within the last 4 months prior to Step 1 registration.

• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to Step 1 registration

• History of any condition that in the opinion of the investigator, would preclude participation in this study

• Current evidence of any of the following:

• Known gastrointestinal disorder affecting absorption of oral medications

• Active uncontrolled infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

• Uncontrolled hypertension

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

• Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is not allowed

• HIV positive with CD4 count < 200 cells/microliter within 30 days prior to registration

• HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. (Note: HIV testing is not required for eligibility for this protocol as it is self-reported.)

• For patients who have not undergone prior Decipher analysis, submission of the specimen to GenomeDx should be as soon as possible after study registration (Step 1) as these results can take up 21 days after the specimen is received at GenomeDx; Step 2 registration must occur within 6 weeks (42 days) of Step 1 registration; if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation

• Patients must not plan to participate in any other clinical trials while receiving treatment on this study or being followed post-protocol therapy.

Related Conditions & MeSH terms

• Adenocarcinoma
• Prostatic Neoplasms
• PSA Progression
• Stage III Prostate Adenocarcinoma
• Stage IV Prostate Adenocarcinoma

Intervention

Drug:
• Apalutamide
Given PO

Radiation:
• External Beam Radiation Therapy
Undergo external beam radiation therapy

Other:
• Placebo
Given PO

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	CIUSSSEMTL-Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
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	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	AdventHealth Altamonte	Altamonte Springs	Florida
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	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	Northside Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Waldo County General Hospital	Belfast	Maine
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Southwestern Vermont Medical Center	Bennington	Vermont
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	James J Peters VA Medical Center	Bronx	New York
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Sands Cancer Center	Canandaigua	New York
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	GenesisCare USA - Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Farmington Health Center	Farmington	Utah
United States	GenesisCare USA - Farmington Hills	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	The West Clinic - Wolf River	Germantown	Tennessee
United States	Arizona Breast Cancer Specialists-Gilbert	Gilbert	Arizona
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
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	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Marin General Hospital	Greenbrae	California
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	The Radiation Oncology Center-Hilton Head/Bluffton	Hilton Head Island	South Carolina
United States	Edward Hines Jr VA Hospital	Hines	Illinois
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
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	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	AdventHealth Kissimmee	Kissimmee	Florida
United States	Sparrow Hospital	Lansing	Michigan
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Logan Regional Hospital	Logan	Utah
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Aurora Saint Luke's 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	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
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	West Virginia University Healthcare	Morgantown	West Virginia
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Stephens Memorial Hospital	Norway	Maine
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	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	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	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Hunter Holmes McGuire Veterans Administration Medical Center	Richmond	Virginia
United States	Reid Health	Richmond	Indiana
United States	Riverton Hospital	Riverton	Utah
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
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	Wilmot Cancer Institute Radiation Oncology at Greece	Rochester	New York
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	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	United 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	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Audie L Murphy VA Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Arizona Breast Cancer Specialists-Scottsdale	Scottsdale	Arizona
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Sidney Kimmel Cancer Center Washington Township	Sewell	New Jersey
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Novant Cancer Institute Radiation Oncology - Supply	Supply	North Carolina
United States	Arizona Center for Cancer Care-Surprise	Surprise	Arizona
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	GenesisCare USA - Troy	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Cancer Treatment Centers of America	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	George Washington University Medical Center	Washington	District of Columbia
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
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	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
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	AdventHealth Winter Park	Winter Park	Florida
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	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
Primary	Biochemical Progression-free survival (bPFS)	bPFS curves will be estimated by the Kaplan-Meier (1958) method and compared between the two treatment arms using a one-sided logrank test at the alpha = 0.12 significance level. Analysis will include evaluation of a potential predictive biomarker (molecular subtype) to inform the design of a subsequent, phase III clinical trial. In addition, a multivariable Cox (1972) regression model will be fit incorporating the three stratification factors used in the randomization (surgical margins, pre-salvage radiation (SRT) PSA, and molecular subtype) as covariates to estimate the adjusted hazard ratio (HR) between the two treatment groups. Additional regression models will be fit including other pretreatment characteristics as covariates.	From randomization to the first occurrence of a rise in PSA, clinical or radiographic local, regional, or distant metastases, or death from any cause, assessed up to 6 years
Secondary	Acute Patient-Reported Morbidity (per the patient reported outcomes [PRO]- Common Terminology Criteria for Adverse Events [CTCAE])	Adverse events will also be assessed using PRO-CTCAE items. Assessments will be collected before and at the end of radiotherapy treatment and in follow-up. For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a chi-square test, or Fisher's exact test if cell frequencies are < 5.	Up to 30 days after radiation therapy
Secondary	Acute Physician-Reported Morbidity (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5)	Adverse events will be scored according to the National Cancer Institute (NCI)'s CTCAE version 5.0. For each type of adverse event, frequencies will be provided for the worst grade experienced by the patient by treatment arm. The proportion of patients with grades >= 1 and >= 3 will be compared between groups using a chi-square test, or Fisher's exact test.	Up to 30 days after radiation therapy
Secondary	Late Patient-Reported Morbidity (per the patient reported outcomes [PRO]- Common Terminology Criteria for Adverse Events [CTCAE])	Adverse events will also be assessed using PRO-CTCAE items. Assessments will be collected before and at the end of radiotherapy treatment and in follow-up. For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a chi-square test, or Fisher's exact test if cell frequencies are < 5.	From the end of radiation therapy + 30 days up to 6 years
Secondary	Late Physician-Reported Morbidity (per the Common Terminology Criteria for Adverse Events [CTCAE] version 4) defined as grade 3+ adverse events occurring more than 30 days after the completion of radiation therapy	Adverse events will be scored according to the NCI's CTCAE version 5.0. For each type of adverse event, counts and frequencies will be provided for the worst grade experienced by the patient by treatment arm. The proportion of patients with grades >= 1 and >= 3 will be compared between groups using a chi-square test, or Fisher's exact test.	From the end of radiation therapy + 30 days to the time of the first recorded late grade 3+ adverse event, assessed up to 6 years
Secondary	Cancer-Specific Mortality (CSM)	CSM will be estimated by the Kaplan-Meier method and compared between treatment arms via the logrank test. Patients dying from other causes will be censored as of the date of death. Cox regression will be used to obtain HRs for this outcome, both unadjusted and adjusted for covariates. A competing risks analysis will also be performed treating death from prostate cancer and death from all other causes as competing risks. Cumulative incidence curves will be generated (Gooley et al., 1999; Dignam et al., 2004) along with 95% confidence intervals and compared between the two treatment arms using Gray's method (Gray, 1988).	From the date of randomization to the date of death due to prostate cancer, assessed up to 6 years
Secondary	Distant Metastasis	Will also be analyzed under a competing risks framework, treating death without experiencing the event in question as a competing risk.	Up to 6 years
Secondary	Initiation of Salvage Hormonal Therapy	Will also be analyzed under a competing risks framework, treating death without experiencing the event in question as a competing risk.	Up to 6 years
Secondary	Local-Regional Progression	Will also be analyzed under a competing risks framework, treating death without experiencing the event in question as a competing risk.	From randomization to local or regional recurrence, assessed up to 6 years
Secondary	Metastasis-Free Survival (MFS)	MFS will be estimated by the Kaplan-Meier method and compared between treatment arms via the logrank test. Cox regression will be used to obtain HRs for this outcome, both unadjusted and adjusted for covariates.	From randomization until distant metastasis (clinical and/or radiographic appearance of disseminated disease) or death from any cause, assessed up to 6 years
Secondary	Overall survival (OS)	OS will be estimated by the Kaplan-Meier method and compared between treatment arms via the logrank test. Cox regression will be used to obtain HRs for this outcome, both unadjusted and adjusted for covariates.	From randomization until death from any cause, assessed up to 6 years
Secondary	PSA Nadir During First Year of Treatment and Prior to Initiation of any Hormonal Salvage Therapy	Will be compared between the two groups using a two-sample t-test.	During first year of treatment
Secondary	Testosterone Levels	Testosterone levels over time will be assessed using mixed effects regression modeling.	Every 3 months until 36 months post randomization
Secondary	Undetectable PSA with a Non-Castrate Testosterone (PSA < 0.1 ng/ml and testosterone >= 50 ng/dl)	The proportion of patients with undetectable PSA and non-castrate testosterone level will be compared between the two treatment arms using chi square tests.	1 year
Secondary	Undetectable PSA with a Non-Castrate testosterone (PSA < 0.1 ng/ml and testosterone >= 50 ng/dl))	The proportion of patients with undetectable PSA and non-castrate testosterone level will be compared between the two treatment arms using chi square tests.	3 years