Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) After Surgery for Men With High-Risk Prostate Cancer, The ERADICATE Study

NCT04484818 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EA8183NCI-2020-02383U10CA180820
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 115

Brief Summary

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 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.

Conditions

Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

• Metastasis-free survival (MFS)

  The primary comparison will be an intention-to-treat analysis of all randomized patients. The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.

  From randomization to development of metastatic disease or death, whichever occurs first, assessed up to 36 months

Secondary Outcomes (9)

• Recurrence-free survival (RFS)

  From randomization to any of the MFS events, pelvic lymph node recurrence or detectable prostate-specific antigen (PSA) (PSA >= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), whichever occurs first, assessed up to 36 months

• Event-free survival

  From randomization to any of the RFS events, treatment with salvage radiation therapy with or without systemic therapy, or initiation of systemic therapy for presumed recurrence, whichever occurs first, assessed up to 36 months

• Overall survival

  From randomization to death by any cause or date last known alive, assessed up to 36 months

• Testosterone recovery rate

  At time of disease progression, assessed up to 36 months

• Time to testosterone recovery

  From randomization to a return of serum testosterone level to greater than or equal to lower limit of normal for the testosterone assay, assessed up to 36 months

Other Outcomes (6)

• Cognitive function

  At 12 months (completion of treatment)

• Change in cognitive function

  Baseline up to 12 months (completion of treatment)

• Identification of novel gene expression signatures

  Up to 36 months

Study Arms (2)

Arm A (ADT, placebo)

ACTIVE COMPARATOR

Patients receive goserelin acetate, leuprolide acetate, or triptorelin 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.

Drug: Goserelin Acetate; Drug: Leuprolide Acetate; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Drug: Triptorelin

Arm B (ADT, darolutamide)

EXPERIMENTAL

Patients receive goserelin acetate, leuprolide acetate, or triptorelin 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.

Drug: Darolutamide; Drug: Goserelin Acetate; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Drug: Triptorelin

Interventions

Darolutamide DRUG

Given PO

Also known as: Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, ODM 201, ODM-201

Arm B (ADT, darolutamide)

Goserelin Acetate DRUG

Given via injection

Also known as: ZDX, Zoladex

Arm A (ADT, placebo); Arm B (ADT, darolutamide)

Leuprolide Acetate DRUG

Given IV

Also known as: A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur

Arm A (ADT, placebo); Arm B (ADT, darolutamide)

Placebo Administration DRUG

Given PO

Arm A (ADT, placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (ADT, placebo); Arm B (ADT, darolutamide)

Triptorelin DRUG

Given via injection

Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, CL-118,532, Detryptoreline

Arm A (ADT, placebo); Arm B (ADT, darolutamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have undergone a radical prostatectomy (RP) and must be registered to step 0 of this study at least 6 weeks after but not more than 16 weeks after their radical prostatectomy
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2
• Patient with a prior or concurrent malignancy within 5 years of registration, 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
• For patients with no previous Decipher score: Tumor tissue specimen from prostatectomy must be available and ready to be shipped
• For patients who have previously had Decipher score performed by Decipher Biosciences, they must have score of \>= 0.6
• For patients who did not have a Decipher score previously performed by Decipher Biosciences, they must have had a Decipher score of \>= 0.6 assessed from the prostatectomy specimen submitted

You may not qualify if:

• Patient must have an undetectable PSA (\< 0.2ng/mL) obtained within 2 weeks prior to randomization
• Leukocytes \>= 3,000/mcL (obtained within 4 weeks prior to registration)
• Absolute neutrophil count \>= 1,000/mcL (obtained within 4 weeks prior to registration)
• Platelets \>= 75,000/mcL (obtained within 4 weeks prior to registration)
• Total bilirubin =\< institutional upper limit of normal (ULN) (obtained within 4 weeks prior to registration)
• 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 registration)
• Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 (obtained within 4 weeks prior to registration)
• 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
• 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
• 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) which must be done before or after prostatectomy prior to randomization. If pre-operative risk does not indicate a need for bone scan, post-operative Decipher score of \>= 0.6 indicates increased risk of metastatic disease and may be used to obtain CT abdomen/pelvis and bone scan prior to randomization

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• ECOG-ACRIN Cancer Research Group: lead

Study Sites (115)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

GenesisCare USA - Lakewood Ranch

Lakewood Rch, Florida, 34202, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

GenesisCare USA - Plantation

Plantation, Florida, 33324, United States

Location

Hawaii Cancer Care Inc - Waterfront Plaza

Honolulu, Hawaii, 96813, United States

Location

Queen's Cancer Cenrer - POB I

Honolulu, Hawaii, 96813, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Straub Clinic and Hospital

Honolulu, Hawaii, 96813, United States

Location

Queen's Cancer Center - Kuakini

Honolulu, Hawaii, 96817, United States

Location

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, 96817, United States

Location

Pali Momi Medical Center

‘Aiea, Hawaii, 96701, United States

Location

Rush - Copley Medical Center

Aurora, Illinois, 60504, United States

Location

Illinois CancerCare-Bloomington

Bloomington, Illinois, 61704, United States

Location

Illinois CancerCare-Canton

Canton, Illinois, 61520, United States

Location

Illinois CancerCare-Carthage

Carthage, Illinois, 62321, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Carle on Vermilion

Danville, Illinois, 61832, United States

Location

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

Location

Crossroads Cancer Center

Effingham, Illinois, 62401, United States

Location

Elmhurst Memorial Hospital

Elmhurst, Illinois, 60126, United States

Location

Illinois CancerCare-Eureka

Eureka, Illinois, 61530, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Illinois CancerCare-Galesburg

Galesburg, Illinois, 61401, United States

Location

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois, 60026, United States

Location

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, 60035, United States

Location

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, 61443, United States

Location

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Illinois CancerCare-Macomb

Macomb, Illinois, 61455, United States

Location

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

Location

Edward Hospital/Cancer Center

Naperville, Illinois, 60540, United States

Location

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, 61350, United States

Location

Illinois CancerCare-Pekin

Pekin, Illinois, 61554, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

Illinois CancerCare-Peru

Peru, Illinois, 61354, United States

Location

Illinois CancerCare-Princeton

Princeton, Illinois, 61356, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Springfield Clinic

Springfield, Illinois, 62702, United States

Location

Memorial Medical Center

Springfield, Illinois, 62781, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

The Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Illinois CancerCare - Washington

Washington, Illinois, 61571, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Medical Oncology and Hematology Associates-West Des Moines

Clive, Iowa, 50325, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Broadlawns Medical Center

Des Moines, Iowa, 50314, United States

Location

Mission Cancer and Blood - Laurel

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Methodist West Hospital

West Des Moines, Iowa, 50266-7700, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Beverly Hospital

Beverly, Massachusetts, 01915, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Addison Gilbert Hospital

Gloucester, Massachusetts, 01930, United States

Location

Lahey Medical Center-Peabody

Peabody, Massachusetts, 01960, United States

Location

Winchester Hospital

Winchester, Massachusetts, 01890, United States

Location

GenesisCare USA - Clarkston

Clarkston, Michigan, 48346, United States

Location

GenesisCare USA - Farmington Hills

Farmington Hills, Michigan, 48334, United States

Location

GenesisCare USA - Macomb

Macomb, Michigan, 48044, United States

Location

GenesisCare USA - Madison Heights

Madison Heights, Michigan, 48071, United States

Location

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, 48073, United States

Location

William Beaumont Hospital - Troy

Troy, Michigan, 48085, United States

Location

GenesisCare USA - Troy

Troy, Michigan, 48098, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Bozeman Deaconess Hospital

Bozeman, Montana, 59715, United States

Location

Benefis Healthcare- Sletten Cancer Institute

Great Falls, Montana, 59405, United States

Location

New Hampshire Oncology Hematology PA-Concord

Concord, New Hampshire, 03301, United States

Location

Solinsky Center for Cancer Care

Manchester, New Hampshire, 03103, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

Location

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

Location

Genesis Healthcare System Cancer Care Center

Zanesville, Ohio, 43701, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Ralph H Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, 76104, United States

Location

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, 75080, United States

Location

Audie L Murphy VA Hospital

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

William S Middleton VA Medical Center

Madison, Wisconsin, 53705, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Marshfield Clinic-Minocqua Center

Minocqua, Wisconsin, 54548, United States

Location

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, 54868, United States

Location

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, 54482, United States

Location

Marshfield Medical Center - Weston

Weston, Wisconsin, 54476, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Goserelin; Leuprolide; luprolide acetate gel depot; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Alicia K Morgans

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 24, 2020
• Study Start: March 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): May 31, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (115)