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

Prostate Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04484818
• Other study ID #: EA8183
• Secondary ID: NCI-2020-02383EA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 1, 2021
• Est. completion date: May 31, 2028

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: May 31, 2028
• Est. primary completion date: May 31, 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Drug:
• Darolutamide
Given PO
• Goserelin Acetate
Given via injection
• Leuprolide Acetate
Given IV
• Placebo Administration
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies

Drug:
• Triptorelin
Given via injection

Locations

Country	Name	City	State
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Beverly Hospital	Beverly	Massachusetts
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	GenesisCare USA - Clarkston	Clarkston	Michigan
United States	Wake Forest University at Clemmons	Clemmons	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	GenesisCare USA - Farmington Hills	Farmington Hills	Michigan
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	GenesisCare USA - Lakewood Ranch	Lakewood Ranch	Florida
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	GenesisCare USA - Macomb	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	William S Middleton VA Medical Center	Madison	Wisconsin
United States	GenesisCare USA - Madison Heights	Madison Heights	Michigan
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Lahey Medical Center-Peabody	Peabody	Massachusetts
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	GenesisCare USA - Plantation	Plantation	Florida
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Audie L Murphy VA Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	City of Hope South Pasadena	South Pasadena	California
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	University of Toledo	Toledo	Ohio
United States	GenesisCare USA - Troy	Troy	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Winchester Hospital	Winchester	Massachusetts
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive function	Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of lifeassessments in the two arms and to evaluate treatment-by-time interactions.	At 12 months (completion of treatment)
Other	Change in cognitive function	Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.	Baseline up to 12 months (completion of treatment)
Other	Identification of novel gene expression signatures	The associations between the gene expression signatures and clinical outcomes will be assessed by Cox proportional hazards models and logrank test.	Up to 36 months
Other	Prognostic value of established signatures	Will include androgen receptor activity, basal-luminal subtyping by modified PAM50 and androgen deprivation therapy score using Cox proportional hazards models. Similar analysis will be performed to evaluate the prognostic value of luminal-basal subtype. The treatment-by-subtype interaction will also be assessed. For androgen deprivation therapy score, patients will be categorized into either low or high androgen deprivation therapy score using a cutoff of 0.36.	Up to 36 months
Other	Decipher scores	Will be associated with MFS as well as disease characteristics. Cox proportional hazards models will be performed with adjustment for important disease characteristics, including prostate-specific antigen, Gleason score, disease stage, pathology of the radical prostatectomy specimen, etc. Decipher score could be categorized into a few risk groups and the Akaike information criterion method will be used to determine the optimal number of cutoff points. To assess whether treatment effect is affected by Decipher score levels, the treatment-by-Decipher interactions will be included in the model as well. Decipher scores range from 0.00 to 1.00, where higher values indicate higher risk disease.	Up to 36 months
Other	Genome-wide alterations	Prostate cancer specimens will be banked for future studies to perform genome-wide alterations in coding and non-coding deoxyribonucleic acid sequences. To identify the genetic alterations that are associated with development of metastasis, Cox proportional hazards models and logrank test will be used. The analysis will focus on actionable alterations first. The treatment-by-alteration interactions will also be assessed to determine whether response to darolutamide is affected by distinct genomic subgroups. Ultimately the findings on gene expression signatures and deoxyribonucleic acid alterations will be assessed in the models simultaneously to identify subsets of patients who might benefit most from the treatment of ADT with or without darolutamide.	Up to 36 months
Primary	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	Recurrence-free survival (RFS)	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 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
Secondary	Event-free survival	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 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
Secondary	Overall survival	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 death by any cause or date last known alive, assessed up to 36 months
Secondary	Testosterone recovery rate	Exact binomial confidence intervals will be used to describe the proportions of patients with testosterone recovery in each arm.	At time of disease progression, assessed up to 36 months
Secondary	Time to testosterone recovery	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 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
Secondary	Incidence of adverse events	Toxicity will be defined using the Common Terminology Criteria for Adverse Events version 5.0.	Up to 78 weeks
Secondary	Change in quality of life: Functional Assessment of Cancer Therapy (FACT)	Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate, FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline, 6, 12 and 18 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.	Baseline up to 18 months
Secondary	Overall quality of life: Functional Assessment of Cancer Therapy (FACT)	Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate total score. The total score can range from 0 to 156, where a higher value indicates a better quality of life. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.	At 18 months
Secondary	Change in Functional Assessment of Cancer Therapy (FACT) - Prostate score	A paired t test will be used to compare Functional Assessment of Cancer Therapy (FACT) - Prostate scores at these two time points in each arm. The total score can range from 0 to 156, where a higher value indicates a better quality of life. A two-sample t test will be performed to compare the changes in FACT - Prostate scores from baseline to 18 months between the two arms. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.	Baseline up to 18 months