Prostate AdenocarcinomaPhase 3NCT05050084
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score, The Guidance Trial
A Phase 3 study testing Bicalutamide, Buserelin and Darolutamide in people with Prostate Adenocarcinoma, run by NRG Oncology at 576 sites in 2 countries.
Trial summary
This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Adenocarcinoma
- What is being tested?
- Bicalutamide, Buserelin and Darolutamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,050 participants
- Where
- 576 sitesin 2 countries
- Study dates
- 6 Dec 2021to 11 Nov 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 270 days prior to registration
- Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
- Has at least one intermediate risk factor (IRF):
- PSA 10-20 ng/mL
- Clinical stage T2b-c (digital rectal examination [DRE] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
- Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological Pathology (ISUP) Grade Group 2-3])
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- Has ONE or more of the following 'unfavorable' intermediate-risk designators:
- > 1 immature reticulocyte fraction (IRF)
- Gleason 4+3=7 (ISUP Grade Group 3)
- >= 50% of biopsy cores positive
- Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s)
- Absence of high-risk features
- Appropriate stage for study entry based on the following diagnostic workup:
- History/physical examination within 120 days prior to registration;
- Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m bone scan or sodium fluoride (NaF) positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities)
- Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1.0 cm in short axis and/or if biopsy is negative.
- Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet pathological criteria based on the latter modalities (e.g. node =< 10 mm in short axis, negative biopsy), the patient will still be eligible
- Age >= 18
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
- Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
- Absolute neutrophil >= 1,000 cells/mm^3 (within 120 days prior to registration)
- Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
- Platelet count >= 100,000 cells/mm^3 independent of transfusion and/or growth factors (within 120 days prior to registration)
- Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
- For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
- Total bilirubin: 1.5 =< institutional upper limit of normal (ULN) (within 120 days prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x institutional ULN (within 120 days prior to registration)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility for this protocol
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
- For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Who cannot join
- Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound [HIFU], laser thermal ablation, etc.) for prostate cancer
- Definitive clinical or radiologic evidence of metastatic disease (M1)
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is not allowed
- Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields
- Previous bilateral orchiectomy
- Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed
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- Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped prior to enrollment on the study with at least a 30 day washout period before baseline study PSA measure and registration
- Active testosterone replacement therapy; any replacement therapy must be stopped at least 30 days prior to registration
- Severe, active co-morbidity defined as follows:
- Current severe or unstable angina;
- New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
- History of any condition that in the opinion of the investigator, would preclude participation in this study
- Inability to swallow oral pills
- High risk features, which includes any of the following:
- Gleason 8-10 [ISUP Grade Group 4-5]
- PSA > 20
- cT3-4 by digital exam OR gross extra-prostatic extension on imaging [indeterminate MRI evidence will not count and the patient will be eligible]
Trial locations and contacts
576 sites in 2 countries.
309 sites in 2 countries
United States300 sites
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
The Queen's Medical Center - West Oahu
‘Ewa Beach, Hawaii, 96706
Summa Health System - Akron Campus
Akron, Ohio, 44304
Cleveland Clinic Akron General
Akron, Ohio, 44307
Lovelace Medical Center-Saint Joseph Square
Albuquerque, New Mexico, 87102
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lovelace Radiation Oncology
Albuquerque, New Mexico, 87109
Presbyterian Kaseman Hospital
Albuquerque, New Mexico, 87110
Saint Luke's Cancer Center - Allentown
Allentown, Pennsylvania, 18104
Alton Memorial Hospital
Alton, Illinois, 62002
UPMC Altoona
Altoona, Pennsylvania, 16601
American Fork Hospital / Huntsman Intermountain Cancer Center
American Fork, Utah, 84003
Veteran's Administration Medical Center - Ann Arbor
Ann Arbor, Michigan, 48105
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Luminis Health Anne Arundel Medical Center
Annapolis, Maryland, 21401
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Ascension Saint Elizabeth Hospital
Appleton, Wisconsin, 54915
Mission Hospital
Asheville, North Carolina, 28801
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806
Grady Health System
Atlanta, Georgia, 30303
Emory Proton Therapy Center
Atlanta, Georgia, 30308
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Piedmont Hospital
Atlanta, Georgia, 30309
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, 95603
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Rush-Copley Medical Center
Aurora, Illinois, 60504
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, 93301
Maryland Proton Treatment Center
Baltimore, Maryland, 21201
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Summa Health System - Barberton Campus
Barberton, Ohio, 44203
Advocate Good Shepherd Hospital
Barrington, Illinois, 60010
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706
Bay Pines VA Healthcare System
Bay Pines, Florida, 33744
Northwell Health Imbert Cancer Center
Bay Shore, New York, 11706
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania, 15009
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Clara Maass Medical Center
Belleville, New Jersey, 07109
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Saint Charles Health System
Bend, Oregon, 97701
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania, 18015
Beverly Hospital
Beverly, Massachusetts, 01915
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Billings Clinic Cancer Center
Billings, Montana, 59101
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina, 29910
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, 80304
Hartford HealthCare - Saint Vincent's Medical Center
Bridgeport, Connecticut, 06606
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Ascension Southeast Wisconsin Hospital - Elmbrook Campus
Brookfield, Wisconsin, 53045
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Crozer-Keystone Regional Cancer Center at Broomall
Broomall, Pennsylvania, 19008
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Roswell Park Cancer Institute
Buffalo, New York, 14263
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, 95682
Illinois CancerCare-Canton
Canton, Illinois, 61520
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Aultman Health Foundation
Canton, Ohio, 44710
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Carlisle Regional Cancer Center
Carlisle, Pennsylvania, 17015
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Duke Cancer Center Cary
Cary, North Carolina, 27518
Sandra L Maxwell Cancer Center
Cedar City, Utah, 84720
Saint Luke's Hospital
Cedar Rapids, Iowa, 52402
Mercy Hospital
Cedar Rapids, Iowa, 52403
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Chambersburg Hospital
Chambersburg, Pennsylvania, 17201
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Northwestern University
Chicago, Illinois, 60611
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657
Adena Regional Medical Center
Chillicothe, Ohio, 45601
Ascension Calumet Hospital
Chilton, Wisconsin, 53014
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
McLaren Cancer Institute-Clarkston
Clarkston, Michigan, 48346
Michigan Healthcare Professionals Clarkston
Clarkston, Michigan, 48346
Case Western Reserve University
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, 21044
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Riverside Methodist Hospital
Columbus, Ohio, 43214
Grant Medical Center
Columbus, Ohio, 43215
Doctors Hospital
Columbus, Ohio, 43228
Memorial Sloan Kettering Commack
Commack, New York, 11725
New Hampshire Oncology Hematology PA-Concord
Concord, New Hampshire, 03301
MD Anderson in The Woodlands
Conroe, Texas, 77384
Mercy Hospital
Coon Rapids, Minnesota, 55433
Mary Imogene Bassett Hospital
Cooperstown, New York, 13326
City of Hope Corona
Corona, California, 92882
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
AMG Crystal Lake - Oncology
Crystal Lake, Illinois, 60014
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Danbury Hospital
Danbury, Connecticut, 06810
Noyes Memorial Hospital/Myers Cancer Center
Dansville, New York, 14437
Carle at The Riverfront
Danville, Illinois, 61832
Geisinger Medical Center
Danville, Pennsylvania, 17822
Emory Decatur Hospital
Decatur, Georgia, 30033
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Advocate Good Samaritan Hospital
Downers Grove, Illinois, 60515
Delaware County Memorial Hospital
Drexel Hill, Pennsylvania, 19026
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Kaiser Permanente Dublin
Dublin, California, 94568
Dublin Methodist Hospital
Dublin, Ohio, 43016
Miller-Dwan Hospital
Duluth, Minnesota, 55805
Saint Luke's Hospital of Duluth
Duluth, Minnesota, 55805
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, 18512
Durham VA Medical Center
Durham, North Carolina, 27705
Duke University Medical Center
Durham, North Carolina, 27710
University of Maryland Shore Medical Center at Easton
Easton, Maryland, 21601
Saint Luke's Hospital-Anderson Campus
Easton, Pennsylvania, 18045
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Shaw Cancer Center
Edwards, Colorado, 81632
Crossroads Cancer Center
Effingham, Illinois, 62401
AtlantiCare Surgery Center
Egg Harbor, New Jersey, 08234
Advocate Sherman Hospital
Elgin, Illinois, 60123
Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus
Elizabeth, New Jersey, 07207
Elmhurst Memorial Hospital
Elmhurst, Illinois, 60126
Arnot Ogden Medical Center/Falck Cancer Center
Elmira, New York, 14905
UC San Diego Health System - Encinitas
Encinitas, California, 92024
Englewood Hospital and Medical Center
Englewood, New Jersey, 07631
Ephrata Cancer Center
Ephrata, Pennsylvania, 17522
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505
Saint Vincent Hospital
Erie, Pennsylvania, 16544
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Farmington Health Center
Farmington, Utah, 84025
Michigan Healthcare Professionals Farmington
Farmington Hills, Michigan, 48334
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121
Piedmont Fayette Hospital
Fayetteville, Georgia, 30214
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
McLaren Cancer Institute-Flint
Flint, Michigan, 48532
MUSC Health Florence Medical Center
Florence, South Carolina, 29505
The New York Hospital Medical Center of Queens
Flushing, New York, 11355
Northwell Health Physicians Partners Radiation Medicine at Queens
Forest Hills, New York, 11375
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
Ascension Saint Francis - Reiman Cancer Center
Franklin, Wisconsin, 53132
Kaiser Permanente-Fremont
Fremont, California, 94538
Washington Hospital
Fremont, California, 94538
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720
Kaiser Permanente-Fresno
Fresno, California, 93720
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Northeast Georgia Medical Center-Gainesville
Gainesville, Georgia, 30501
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022
Adams Cancer Center
Gettysburg, Pennsylvania, 17325
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Arizona Center for Cancer Care - Gilbert
Gilbert, Arizona, 85297
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, 21061
Crozer Regional Cancer Center at Brinton Lake
Glen Mills, Pennsylvania, 19342
Glens Falls Hospital
Glens Falls, New York, 12801
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Addison Gilbert Hospital
Gloucester, Massachusetts, 01930
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Altru Cancer Center
Grand Forks, North Dakota, 58201
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Banner North Colorado Medical Center
Greeley, Colorado, 80631
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Bellin Memorial Hospital
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Marin General Hospital
Greenbrae, California, 94904
Northwell Health Cancer Institute at Huntington
Greenlawn, New York, 11740
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601
Saint Francis Hospital
Greenville, South Carolina, 29601
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830
Self Regional Healthcare
Greenwood, South Carolina, 29646
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
The Cancer Institute of New Jersey Hamilton
Hamilton, New Jersey, 08690
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Hartford Hospital
Hartford, Connecticut, 06102
Advocate South Suburban Hospital
Hazel Crest, Illinois, 60429
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, 80129
The Radiation Oncology Center-Hilton Head/Bluffton
Hilton Head Island, South Carolina, 29926
Edward Hines Jr VA Hospital
Hines, Illinois, 60141
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
UT MD Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
IRMC Cancer Center
Indiana, Pennsylvania, 15701
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
City of Hope at Irvine Lennar
Irvine, California, 92618
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Jersey City Medical Center
Jersey City, New Jersey, 07302
Emory Johns Creek Hospital
Johns Creek, Georgia, 30097
University of Wisconsin Carbone Cancer Center - Johnson Creek
Johnson Creek, Wisconsin, 53038
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Johnstown, Pennsylvania, 15901
Jupiter Medical Center
Jupiter, Florida, 33458
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
University of Kansas Cancer Center
Kansas City, Kansas, 66160
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, 53142
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
City of Hope Antelope Valley
Lancaster, California, 93534
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446
UM Capital Region Medical Center
Largo, Maryland, 20774
UT MD Anderson - League City
League City, Texas, 77573
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Sechler Family Cancer Center
Lebanon, Pennsylvania, 17042
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
Saint Joseph Radiation Oncology Resource Center
Lexington, Kentucky, 40504
AMG Libertyville - Oncology
Libertyville, Illinois, 60048
Condell Memorial Hospital
Libertyville, Illinois, 60048
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Logan Regional Hospital
Logan, Utah, 84321
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Medical Center of the Rockies
Loveland, Colorado, 80538
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado, 80539
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Michigan Healthcare Professionals Macomb
Macomb, Michigan, 48044
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Michigan Healthcare Professionals Madison Heights
Madison Heights, Michigan, 48071
Solinsky Center for Cancer Care
Manchester, New Hampshire, 03103
OhioHealth Mansfield Hospital
Mansfield, Ohio, 44903
Cleveland Clinic Cancer Center Mansfield
Mansfield, Ohio, 44906
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin, 54143
OhioHealth Marion General Hospital
Marion, Ohio, 43302
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Fremont - Rideout Cancer Center
Marysville, California, 95901
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124
Loyola University Medical Center
Maywood, Illinois, 60153
Yolanda G Barco Oncology Institute
Meadville, Pennsylvania, 16335
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania, 17050
Summa Health Medina Medical Center
Medina, Ohio, 44256
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060
Ascension Columbia Saint Mary's Hospital Ozaukee
Mequon, Wisconsin, 53097
Canada9 sites
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Québec, Quebec, G1R 2J6
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Atlantic Health Sciences Corporation-Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)
This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Decipher score in this study is used for patient selection and the two variations of treatment to be studied: intensification for higher Decipher score or de-intensification for low Decipher score. Patients with higher Decipher risk score will be assigned to the part of the study that compares the use of 6 months of the usual treatment (hormone therapy and radiation treatment) to the use of darolutamide plus the usual treatment (intensification). The purpose of this section of the study is to determine whether the additional drug can reduce the chance of cancer coming back and spreading in patients with higher Decipher score. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. Alternatively, patients with low Decipher risk score will be assigned to the part of the study that compares the use of radiation treatment alone (de-intensification) to the usual approach (6 months of hormone therapy plus radiation). The purpose of this part of the study is to determine if radiation treatment alone is as effective compared to the usual treatment without affecting the chance of tumor coming back in patients with low Decipher score prostate cancer. Radiation therapy uses high energy to kill tumor cells and reduce the tumor size. Hormone therapy drugs such as darolutamide suppress or block the production or action of male hormones that play role in prostate cancer development. Effect of radiation treatment alone in patients with low Decipher score prostate cancer could be the same as the usual approach in stabilizing prostate cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score < 0.40) treated with radiation therapy (RT) alone instead of 6 months androgen deprivation therapy (ADT) + RT experience non-inferior rate of distant metastasis. (De-intensification study) II. To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score >= 0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT. (Intensification study)
SECONDARY OBJECTIVES:
- To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
II. To compare time to prostate specific antigen (PSA) failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
III. To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone).
IV. To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
- To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions.
VI. To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide).
VII. To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
VIII. To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
IX. To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
- To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
XI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
EXPLORATORY OBJECTIVES:
- To compare changes in cardio-metabolic markers, including body mass index, lipids, blood glucose, complete blood count (CBC), comprehensive metabolic panel (CMP), and hemoglobin (Hgb) A1c, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
II. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
III. To compare cumulative incidence of locoregional failure based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
IV. To compare castrate-resistant prostate cancer (CRPC) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
- To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
VI. To compare time to testosterone recovery (defined as a T > 200ng/dL) between the standard of care (RT plus 6 months of ADT) and intensification (RT plus 6 months of ADT plus darolutamide) interventions.
VII. To compare health utilities, as measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
VIII. To develop and assess a machine learning/artificial intelligence algorithm for radiotherapy planning and/or quality assurance.
IX. To perform future translational correlative studies using biological data, Decipher results, and clinical outcomes.
OUTLINE:
DE-INTENSIFICATION STUDY: Patients with Decipher score < 0.40 are randomized to 1 of 2 arms.
ARM I: Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.
INTENSIFICATION STUDY: Patients with Decipher score >= 0.40 are randomized to 1 of 2 arms.
ARM III: Patients receive treatment as in Arm II.
ARM IV: Patients receive RT and ADT as in Arm II. Patients also receive darolutamide orally (PO) twice daily (BID). Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 12, 24, 36, 48 and 60 months.
- Conditions
- Prostate Adenocarcinoma
- Being tested
- Bicalutamide, Buserelin, Darolutamide, Degarelix, Flutamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BicalutamideDrug
Also called Casodex, Cassotide, Cosudex, ICI 176,334
Drug
BuserelinDrug
Also called 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig), BSRL, Busereline, Etilamide
Drug
DarolutamideDrug
Also called Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788
Given PO
DegarelixDrug
Also called ASP 3550, ASP-3550, ASP3550, FE 200486
Drug
FlutamideDrug
Also called 4'-Nitro-3'-trifluoromethylisobutyranilide, Apimid, Cebatrol, Chimax
Drug
GoserelinDrug
Also called ICI-118630
Drug
HistrelinDrug
Drug
LeuprolideDrug
Also called Leuprorelin
Drug
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo RT
RelugolixDrug
Also called N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385
Drug
TriptorelinDrug
Also called 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY 25650, AY-25650
Drug
| Study group | Role | What they receive |
|---|---|---|
| Arm I (RT) | Experimental | Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity. Receives: Radiation: Radiation Therapy |
| Arm II (RT, ADT) | Experimental | Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days. Receives: Drug: Bicalutamide; Drug: Buserelin; Drug: Degarelix; Drug: Flutamide; Drug: Goserelin; Drug: Histrelin; Drug: Leuprolide; Radiation: Radiation Therapy; Drug: Relugolix; Drug: Triptorelin |
| Arm III (RT, ADT) | Experimental | Patients receive treatment as in Arm II. Receives: Drug: Bicalutamide; Drug: Buserelin; Drug: Degarelix; Drug: Flutamide; Drug: Goserelin; Drug: Histrelin; Drug: Leuprolide; Radiation: Radiation Therapy; Drug: Relugolix; Drug: Triptorelin |
| Arm IV (RT, ADT, darolutamide) | Experimental | Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Buserelin; Drug: Darolutamide; Drug: Degarelix; Drug: Goserelin; Drug: Histrelin; Drug: Leuprolide; Radiation: Radiation Therapy; Drug: Relugolix; Drug: Triptorelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distant metastasis (DM) (De-intensification study)
Measured: From randomization to the detection of distant metastasis by conventional imaging, assessed up to 5 years
Metastasis-free survival (MFS) (Intensification study)
MFS will be estimated by the Kaplan-Meier (1958) method and compared between the two treatment arms using a stratified log-rank test (stratified by the randomization stratification factors) at one-sided alpha level of 0.025.
Measured: From randomization until the occurrence of distant metastasis by conventional imaging or death from any cause, assessed up to 5 years
Secondary outcomes (11)
Overall survival
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test. Cox regression models will also be fit, adjusted for the stratification factors, to estimate hazard ratios, together with 95% confidence intervals.
Measured: From randomization to death from any cause, assessed up to 5 years
Time to prostate specific antigen (PSA) failure
Defined as PSA > 2 ng/ml above the nadir post randomization. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Measured: Up to 5 years
MFS (De-intensification study)
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test. Cox regression models will also be fit, adjusted for the stratification factors, to estimate hazard ratios, together with 95% confidence intervals.
Measured: From randomization until the occurrence of distant metastasis by conventional imaging or death from any cause, assessed up to 5 years
MFS including positron emission tomography (PET) imaging
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test.
Measured: From randomization until the occurrence of distant metastasis by conventional and/or molecular imaging or death from any cause, assessed up to 5 years
Locoregional failure (LRF)
Will compare cumulative incidence between arms.
Measured: From randomization until local or regional recurrence based upon conventional imaging or biopsy, assessed up to 5 years
DM including PET imaging
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Measured: From randomization to the detection of distant metastasis by conventional and/or molecular imaging, assessed up to 5 years
Prostate cancer-specific mortality
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case death from causes other than prostate cancer as the competing risk.
Measured: From randomization until death from prostate cancer, assessed up to 5 years
Sexual and hormonal function related quality of life
Measured by the Expanded Prostate Cancer Index Composite-26 (EPIC-26).
Measured: Up to 5 years
Fatigue
Measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument.
Measured: Up to 5 years
Cognition
Measured by the Functional Assessment of Chronic illness Therapy-Cognitive (FACT-Cog).
Measured: Up to 5 years
DM (Intensification study)
Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.
Measured: From randomization to the detection of distant metastasis by conventional imaging, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2021
- Study start6 Dec 2021
- Primary completion11 Nov 2026 (estimated)
- Study completion11 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,050 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Neil B Desai, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05050084
- Sponsor's protocol ID
- NRG-GU010
- Other IDs
- NCI-2021-08760, NRG-GU010, NRG-GU010, U10CA180868
- Status last verified
- Aug 2026
- First submitted
- 9 Sep 2021
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.