Prostate Cancer
EA8183 / ERADICATE
Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) after Surgery for Men with High-Risk Prostate Cancer, The ERADICATE Study
STATUS: Closed to Accrual and Intervention
This phase III trial compares the effect of adding darolutamide to ADT versus ADT alone after surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It also plays a role in prostate cancer development. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from returning compared to ADT alone in patients with prostate cancer.
- PRE-REGISTRATION INCLUSION (STEP 0)
- Patient must be >= 18 years of age
- Patient must have undergone a radical prostatectomy (RP) completed at least 2 weeks prior to Step 0 pre-registration. Patient must also meet one of the following criteria: * For patients with a Decipher score obtained through standard of care testing outside the protocol prior to registration to Step 0: ** The Decipher score must be > 0.6. ** The patient must be registered to Step 0 no later than 24 weeks (168 days) after surgery. ** The Decipher Score assay results and report must be available for upload to Medidata Rave prior to proceeding to Step 1 Randomization * For patients without a previous Decipher score performed through standard of care testing outside the protocol prior to registration to Step 0 ** The patient must be registered to Step 0 no later than 19 weeks (133 days) after surgery to allow time to have tissue submitted and tested before proceeding to Step 1 randomization. ** The patient must have a Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score >= 3. The CAPRA-S score is calculated by assigning points for PSA in ng/mL, Gleason score, surgical margin status, seminal vesicle invasion, and extra-capsular extension. Lymph node involvement will serve as an exclusion criteria and will not count towards CAPRA-S inclusion score. ** Tumor tissue specimen from radical prostatectomy must be available and ready to be shipped within 20 weeks post-surgery. * NOTE: Every effort should be made to submit adequate tumor tissue specimen to Decipher Biosciences for testing immediately. Decipher Biosciences will notify submitting institution of Decipher score results within 21 days of receipt of adequate tumor tissue specimens. Failure to submit adequate tissue will result in request for additional tissue and delays in testing and reporting
- PRE-REGISTRATION EXCLUSION (STEP 0)
- Patient must not have any previous treatment with androgen deprivation therapy (ADT), chemotherapy, or other physician prescribed systemic therapy for treatment of their prostate cancer * NOTE: Prior treatment with bicalutamide is permitted
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
- INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
- Patient must be randomized to Step 1 a minimum of 6 weeks and a maximum of 24 weeks (168 days) from radical prostatectomy (RP)
- For patients who did not have a Decipher score obtained through standard of care testing outside of the protocol prior to registration to Step 0, the Decipher score is > 0.6 assessed from the prostatectomy specimen submitted
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2
- Patients with a prior or concurrent malignancy within 5 years of Step 1 randomization, 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
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- 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
- Patient must be able to take oral medications
- Patient must have a PSA < 0.2 ng/mL obtained within 2 weeks prior to Step 1 randomization
- Patient must not have pre or post-operative radiographic evidence of cancer recurrence or metastasis by abdominal and pelvic imaging (computed tomography [CT] abdomen/pelvis, whole body magnetic resonance imaging [MRI], MRI abdomen/pelvis, or equivalent, AND bone scan) within 24 weeks (168 days) prior to Step 1 randomization. If pre-operative risk does not support a need for CT abdomen/pelvis and/or bone scan imaging, the lack of baseline imaging due to low risk disease should be documented. * NOTE: A post-operative Decipher Score of > 0.6 indicates an increased risk of metastatic disease and a bone scan or CT scan is required prior to Step 1 randomization
- Due to the potential harm through seminal transfer to an unborn fetus with the treatment regimens being used, sexually active patients must not expect to father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 28 days after the last dose of protocol treatment
- Leukocytes >= 3,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
- Absolute neutrophil count (ANC) >= 1,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
- Platelets >= 75,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
- Hemoglobin (Hgb) > 8 g/dL (obtained within 4 weeks prior to Step 1 randomization)
- Total bilirubin =< institutional upper limit of normal (ULN) (or =< 3 x ULN for patients with known Gilbert’s disease) (obtained within 4 weeks prior to Step 1 randomization)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to Step 1 randomization)
- Glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2 estimated by Modification of Diet in Renal Disease (MDRD) formula (obtained within 4 weeks prior to Step 1 randomization)
- EXCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
- Patient must not have pathologic evidence of pelvic lymph node involvement
- Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
United States
CA
Duarte
City of Hope Comprehensive Cancer Center
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Email: becomingapatient@coh.org
Los Angeles
Los Angeles General Medical Center
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USC / Norris Comprehensive Cancer Center
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Palo Alto
Stanford Cancer Institute Palo Alto
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Email: ccto-office@stanford.edu
VA Palo Alto Health Care System
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South Pasadena
City of Hope South Pasadena
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Email: becomingapatient@coh.org
Upland
City of Hope Upland
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CT
Hartford
Hartford Hospital
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FL
Lakewood Ranch
GenesisCare USA - Lakewood Ranch
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Miami Beach
Mount Sinai Medical Center
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Email: yenrique@msmc.com
Plantation
GenesisCare USA - Plantation
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Email: Rudi.Ross@usa.genesiscare.com
HI
Aiea
Hawaii Cancer Care - Westridge
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Email: info@hawaiicancercare.com
Pali Momi Medical Center
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Honolulu
Hawaii Cancer Care Inc - Waterfront Plaza
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Email: i.webster@hawaiicancercare.com
Queen's Cancer Cenrer - POB I
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Queen's Cancer Center - Kuakini
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Queen's Medical Center
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Straub Clinic and Hospital
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The Cancer Center of Hawaii-Liliha
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IA
Clive
Mission Cancer and Blood - West Des Moines
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Des Moines
Broadlawns Medical Center
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Iowa Lutheran Hospital
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Iowa Methodist Medical Center
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Mission Cancer and Blood - Des Moines
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Mission Cancer and Blood - Laurel
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West Des Moines
Methodist West Hospital
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ID
Coeur D'Alene
Kootenai Health - Coeur d'Alene
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Email: mccinfo@mtcancer.org
IL
Aurora
Rush - Copley Medical Center
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Email: Cancer.Research@rushcopley.com
Bloomington
Illinois CancerCare-Bloomington
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Email: andersonj@illinoiscancercare.com
Canton
Illinois CancerCare-Canton
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Carthage
Illinois CancerCare-Carthage
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Chicago
Northwestern University
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Email: cancer@northwestern.edu
University of Chicago Comprehensive Cancer Center
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Email: cancerclinicaltrials@bsd.uchicago.edu
Danville
Carle at The Riverfront
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Email: Research@carle.com
Decatur
Cancer Care Specialists of Illinois - Decatur
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Email: morganthaler.jodi@mhsil.com
Decatur Memorial Hospital
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Email: morganthaler.jodi@mhsil.com
Effingham
Carle Physician Group-Effingham
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Email: Research@carle.com
Crossroads Cancer Center
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Email: morganthaler.jodi@mhsil.com
Elmhurst
Elmhurst Memorial Hospital
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Email: Jrohde@emhc.org
Eureka
Illinois CancerCare-Eureka
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Email: andersonj@illinoiscancercare.com
Evanston
NorthShore University HealthSystem-Evanston Hospital
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Galesburg
Illinois CancerCare-Galesburg
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Glenview
NorthShore University HealthSystem-Glenbrook Hospital
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Highland Park
NorthShore University HealthSystem-Highland Park Hospital
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Kewanee
Illinois CancerCare-Kewanee Clinic
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Email: andersonj@illinoiscancercare.com
Lake Forest
Northwestern Medicine Lake Forest Hospital
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Email: cancertrials@northwestern.edu
Macomb
Illinois CancerCare-Macomb
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Email: andersonj@illinoiscancercare.com
Mattoon
Carle Physician Group-Mattoon/Charleston
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Email: Research@carle.com
Naperville
Edward Hospital/Cancer Center
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New Lenox
UC Comprehensive Cancer Center at Silver Cross
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Email: cancerclinicaltrials@bsd.uchicago.edu
Ottawa
Illinois CancerCare-Ottawa Clinic
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Pekin
Illinois CancerCare-Pekin
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Peoria
Illinois CancerCare-Peoria
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Methodist Medical Center of Illinois
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Peru
Illinois CancerCare-Peru
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Princeton
Illinois CancerCare-Princeton
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Springfield
Memorial Medical Center
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Email: pallante.beth@mhsil.com
Southern Illinois University School of Medicine
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Springfield Clinic
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Urbana
Carle Cancer Center
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Email: Research@carle.com
The Carle Foundation Hospital
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Washington
Illinois CancerCare - Washington
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Email: andersonj@illinoiscancercare.com
IN
Indianapolis
Indiana University/Melvin and Bren Simon Cancer Center
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Email: iutrials@iu.edu
MA
Beverly
Beverly Hospital
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Burlington
Lahey Hospital and Medical Center
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Email: lhmc-cancer-clinical-trials@lahey.org
Gloucester
Addison Gilbert Hospital
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Peabody
Lahey Medical Center-Peabody
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Email: lhmc-cancer-clinical-trials@lahey.org
Winchester
Winchester Hospital
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Email: ctsucontact@westat.com
MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
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Email: jhcccro@jhmi.edu
MI
Clarkston
Michigan Healthcare Professionals Clarkston
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Farmington Hills
Michigan Healthcare Professionals Farmington
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Macomb
Michigan Healthcare Professionals Macomb
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Madison Heights
Michigan Healthcare Professionals Madison Heights
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Royal Oak
Corewell Health William Beaumont University Hospital
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Troy
Corewell Health Beaumont Troy Hospital
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Michigan Healthcare Professionals Troy
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Email: Rudi.Ross@usa.genesiscare.com
MN
Fridley
Unity Hospital
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Email: mmcorc@healthpartners.com
Maplewood
Minnesota Oncology Hematology PA-Maplewood
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Email: mmcorc@healthpartners.com
Minneapolis
Hennepin County Medical Center
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Email: mmcorc@healthpartners.com
Saint Paul
Regions Hospital
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MO
Cape Girardeau
Saint Francis Medical Center
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Email: sfmc@sfmc.net
Saint Louis
Mercy Hospital Saint Louis
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MT
Bozeman
Bozeman Health Deaconess Hospital
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Email: mccinfo@mtcancer.org
Great Falls
Benefis Sletten Cancer Institute
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Email: mccinfo@mtcancer.org
NC
Clemmons
Wake Forest University at Clemmons
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Winston-Salem
Wake Forest University Health Sciences
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ND
Bismarck
Sanford Bismarck Medical Center
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Fargo
Sanford Broadway Medical Center
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Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Sanford Roger Maris Cancer Center
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Email: OncologyClinicalTrialsFargo@sanfordhealth.org
NH
Concord
New Hampshire Oncology Hematology PA-Concord
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Manchester
Solinsky Center for Cancer Care
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NY
Bronx
Montefiore Medical Center-Einstein Campus
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Email: eskwak@montefiore.org
OH
Cincinnati
University of Cincinnati Cancer Center-UC Medical Center
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Email: cancer@uchealth.com
Toledo
University of Toledo
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West Chester
University of Cincinnati Cancer Center-West Chester
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Email: cancer@uchealth.com
Zanesville
Genesis Healthcare System Cancer Care Center
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Email: sheree@columbusccop.org
OK
Oklahoma City
University of Oklahoma Health Sciences Center
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Email: ou-clinical-trials@ouhsc.edu
PA
Bryn Mawr
Bryn Mawr Hospital
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Danville
Geisinger Medical Center
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Email: HemonCCTrials@geisinger.edu
Hershey
Penn State Milton S Hershey Medical Center
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Email: CTO@hmc.psu.edu
Media
Riddle Memorial Hospital
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Email: turzoe@mlhs.org
West Reading
Reading Hospital
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Wilkes-Barre
Geisinger Wyoming Valley/Henry Cancer Center
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Email: HemonCCTrials@geisinger.edu
Wynnewood
Lankenau Medical Center
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Email: turzoe@mlhs.org
SC
Charleston
Medical University of South Carolina
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Email: hcc-clinical-trials@musc.edu
Ralph H Johnson VA Medical Center
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Email: ashley.salvo@va.gov
TX
Dallas
Parkland Memorial Hospital
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Email: canceranswerline@UTSouthwestern.edu
UT Southwestern/Simmons Cancer Center-Dallas
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Email: canceranswerline@UTSouthwestern.edu
Fort Worth
UT Southwestern/Simmons Cancer Center-Fort Worth
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Email: canceranswerline@UTSouthwestern.edu
Richardson
UT Southwestern Clinical Center at Richardson/Plano
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Email: Suzanne.cole@utsouthwestern.edu
San Antonio
Audie L Murphy VA Hospital
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University of Texas Health Science Center at San Antonio
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Email: phoresearchoffice@uthscsa.edu
VA
Richmond
Virginia Commonwealth University/Massey Cancer Center
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Email: CTOclinops@vcu.edu
WI
Antigo
Langlade Hospital and Cancer Center
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Email: Juli.Alford@aspirus.org
Eau Claire
Marshfield Medical Center-EC Cancer Center
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Email: oncology.clinical.trials@marshfieldresearch.org
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
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William S Middleton VA Medical Center
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Marshfield
Marshfield Medical Center-Marshfield
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Email: oncology.clinical.trials@marshfieldresearch.org
Minocqua
Marshfield Clinic-Minocqua Center
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Email: oncology.clinical.trials@marshfieldresearch.org
Rice Lake
Marshfield Medical Center-Rice Lake
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Email: oncology.clinical.trials@marshfieldresearch.org
Stevens Point
Ascension Saint Michael's Hospital
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Email: Beth.Knetter@aspirus.org
Marshfield Medical Center-River Region at Stevens Point
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Email: oncology.clinical.trials@marshfieldresearch.org
Wausau
Aspirus Regional Cancer Center
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Weston
Marshfield Medical Center - Weston
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Email: oncology.clinical.trials@marshfieldresearch.org
Wisconsin Rapids
Aspirus Cancer Care - Wisconsin Rapids
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PRIMARY OBJECTIVE: I. To determine whether 12 months (48 weeks) of androgen deprivation therapy (ADT) and darolutamide improves metastasis-free survival (MFS) compared to 12 months (48 weeks) of ADT plus placebo in men with high risk prostate cancer (defined by Cancer of the Prostate Risk Assessment Post-surgical [CAPRA-S] score >= 3 and a high Decipher score (> 0.6) [C3+D+]) that have undergone radical prostatectomy. SECONDARY OBJECTIVES: I. To determine whether 12 months (48 weeks) of ADT and darolutamide improves recurrence-free survival (RFS) compared to 12 months (48 weeks) of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy. II. To determine whether 12 months (48 weeks) of ADT and darolutamide improves event-free survival (EFS) compared to 12 months (48 weeks) of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy. III. To determine whether 12 months (48 weeks) of ADT and darolutamide improves overall survival (OS) compared to 12 months (48 weeks) of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy. IV. To determine the rate of testosterone recovery and time to testosterone recovery in each treatment arm. V. To evaluate the safety and tolerability of ADT and darolutamide. CORRELATIVE OBJECTIVES FOR EXPLORATORY BIOMARKERS: I. To discover a novel gene expression signature in the Decipher transcriptome platforms that is predictive of clinical outcome, as defined by the primary and secondary objectives of this study, in response to ADT by intensification with darolutamide versus ADT alone. II. To assess the prevalence of subclasses of established transcriptome expression signatures and prospectively validate their predictive value for ADT response, these include: (i) androgen receptor (AR) activity (ii) Basal-luminal subtyping based on modified PAM50, and (iii) ADT score. III. To assess whether the spectrum of high Decipher scores (> 0.6-1.0), prostate-specific antigen (PSA) levels at presentation and post-radical prostatectomy and final pathology variables affect the response and outcome to ADT and darolutamide. QUALITY OF LIFE (QOL) OBJECTIVES: I. To compare overall quality of life, measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, at 12 months (48 weeks) between the two arms. (Primary) II. To compare the change in overall quality of life, measured by FACT-P total score, from baseline to 12 months (48 weeks) between the two arms. (Secondary) III. To compare patient-reported fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scores) at 12 months (48 weeks) between the two treatment arms. (Secondary) IV. To compare the change in subjective patient-reported cognitive function (FACT-Cognitive [Cog]) from baseline to 12 months (48 weeks) between the treatment arms. (Exploratory) V. To compare subjective patient-reported cognitive function (FACT-Cog scores) at 12 months (48 weeks) between the two treatment arms. (Exploratory) OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive goserelin acetate, leuprolide acetate, triptorelin, or degarelix via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive goserelin acetate, leuprolide acetate, triptorelin, or degarelix via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 36 months.
Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.
The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.