Clinical trial NCT04484818: Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) After Surgery for Men With High-Risk Prostate Cancer, The ERADICATE Study
Official title: A Phase III Double Blinded Study of Early Intervention After RADICAl ProstaTEctomy With Androgen Deprivation Therapy With or Without Darolutamide vs. Placebo in Men at Highest Risk of Prostate Cancer Metastasis by Genomic Stratification (ERADICATE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostate Carcinoma
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-07-24
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVE:

I. To determine whether 12 months of androgen deprivation therapy (ADT) and darolutamide improves metastasis-free survival (MFS) compared to 12 months 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) \[C3+D+\]) who have undergone radical prostatectomy.

SECONDARY OBJECTIVES:

I. To determine whether 12 months of ADT and darolutamide improves recurrence-free survival (RFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy.

II. To determine whether 12 months of ADT and darolutamide improves event-free survival (EFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy.

III. To determine whether 12 months of ADT and darolutamide improves overall survival (OS) compared to 12 months 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 (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 (RP) 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 18 months between the two arms. (Primary) II. To compare the change in overall quality of life, measured by FACT-P total score, from baseline to 18 months between the two arms. (Secondary) III. To compare patient-reported fatigue (Functional Assessment of Chronic Illness Therapy \[FACIT\]-Fatigue scores) at 12 months 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 between the treatment arms. (Exploratory) V. To compare subjective patient-reported cognitive function (FACT-Cog scores) at 12 months between the two treatment arms. (Exploratory)

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: 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.

ARM II: 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.

After completion of study treatment, patients are followed up every 3 months for 36 months.

Eligibility criteria: Inclusion Criteria:

* PRE-REGISTRATION INCLUSION (STEP 0)
* 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
* INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
* 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
* For patients who did not have a Decipher score previously performed by Decipher Biosciences, patients must also have a CAPRA-S score \>= 3. The CAPRA-S score is calculated by assigning points for PSA in ng/mL, 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. A CAPRA-S score is not required for patients who had a Decipher score previously performed by Decipher Biosciences
* 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)

Exclusion Criteria:

* 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
* 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
* EXCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
* 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

Primary outcomes:
measure: Metastasis-free survival (MFS)
timeFrame: From randomization to development of metastatic disease or death, whichever occurs first, assessed up to 36 months
Secondary outcomes:
measure: Recurrence-free survival (RFS)
timeFrame: 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
measure: Event-free survival
timeFrame: 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
measure: Overall survival
timeFrame: From randomization to death by any cause or date last known alive, assessed up to 36 months
measure: Testosterone recovery rate
timeFrame: At time of disease progression, assessed up to 36 months
measure: Time to testosterone recovery
timeFrame: 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
measure: Incidence of adverse events
timeFrame: Up to 78 weeks
measure: Change in quality of life: Functional Assessment of Cancer Therapy (FACT)
timeFrame: Baseline up to 18 months
measure: Overall quality of life: Functional Assessment of Cancer Therapy (FACT)
timeFrame: At 18 months
measure: Change in Functional Assessment of Cancer Therapy (FACT) - Prostate score
timeFrame: Baseline up to 18 months
Other outcomes:
measure: Cognitive function
timeFrame: At 12 months (completion of treatment)
measure: Change in cognitive function
timeFrame: Baseline up to 12 months (completion of treatment)
measure: Identification of novel gene expression signatures
timeFrame: Up to 36 months
measure: Prognostic value of established signatures
timeFrame: Up to 36 months
measure: Decipher scores
timeFrame: Up to 36 months
measure: Genome-wide alterations
timeFrame: Up to 36 months
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: South Pasadena
country: United States
facility: City of Hope South Pasadena
state: California
city: Upland
country: United States
facility: City of Hope Upland
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Lakewood Ranch
country: United States
facility: GenesisCare USA - Lakewood Ranch
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Plantation
country: United States
facility: GenesisCare USA - Plantation
state: Florida
city: 'Aiea
country: United States
facility: Pali Momi Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc - Waterfront Plaza
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Cenrer - POB I
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Center - Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Danville
country: United States
facility: Carle on Vermilion
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Elmhurst
country: United States
facility: Elmhurst Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem-Glenbrook Hospital
state: Illinois
city: Highland Park
country: United States
facility: NorthShore University HealthSystem-Highland Park Hospital
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Lake Forest
country: United States
facility: Northwestern Medicine Lake Forest Hospital
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital/Cancer Center
state: Illinois
city: New Lenox
country: United States
facility: UC Comprehensive Cancer Center at Silver Cross
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Urbana
country: United States
facility: The Carle Foundation Hospital
state: Illinois
city: Washington
country: United States
facility: Illinois CancerCare - Washington
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Broadlawns Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mission Cancer and Blood - Laurel
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: West Des Moines
country: United States
facility: Methodist West Hospital
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Beverly
country: United States
facility: Beverly Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Gloucester
country: United States
facility: Addison Gilbert Hospital
state: Massachusetts
city: Peabody
country: United States
facility: Lahey Medical Center-Peabody
state: Massachusetts
city: Winchester
country: United States
facility: Winchester Hospital
state: Massachusetts
city: Clarkston
country: United States
facility: GenesisCare USA - Clarkston
state: Michigan
city: Farmington Hills
country: United States
facility: GenesisCare USA - Farmington Hills
state: Michigan
city: Macomb
country: United States
facility: GenesisCare USA - Macomb
state: Michigan
city: Madison Heights
country: United States
facility: GenesisCare USA - Madison Heights
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Troy
country: United States
facility: GenesisCare USA - Troy
state: Michigan
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Concord
country: United States
facility: New Hampshire Oncology Hematology PA-Concord
state: New Hampshire
city: Manchester
country: United States
facility: Solinsky Center for Cancer Care
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: Clemmons
country: United States
facility: Wake Forest University at Clemmons
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System Cancer Care Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H Johnson VA Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: UT Southwestern/Simmons Cancer Center-Fort Worth
state: Texas
city: Richardson
country: United States
facility: UT Southwestern Clinical Center at Richardson/Plano
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy VA Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Eau Claire
country: United States
facility: Marshfield Medical Center-EC Cancer Center
state: Wisconsin
city: Madison
country: United States
facility: William S Middleton VA Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center-Marshfield
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic-Minocqua Center
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Medical Center-Rice Lake
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Medical Center-River Region at Stevens Point
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Medical Center - Weston
state: Wisconsin
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Alicia K Morgans
role: PRINCIPAL_INVESTIGATOR
References: