LHRH Analogue Therapy With Enzalutamide or Bicalutamide i... | NCT02058706

NCT02058706

Secondary IDs

ID	Type	Description	Link
NCI-2014-00212	Registry Identifier	CTRP (Clinical Trial Reporting Program)
2013-083	Other Identifier	Barbara Ann Karmanos Cancer Institute
P30CA022453	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
National Cancer Institute (NCI)	NIH

Oversight Module

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the rates of achieving prostate-specific antigen (PSA) remission at month 7 with LHRH analogue therapy and enzalutamide (Arm A) with that achieved with LHRH analogue and bicalutamide (Arm B) in metastatic hormone sensitive prostate cancer.

SECONDARY OBJECTIVES:

I. To compare the primary endpoint by race. II. To compare the rates of each of 2 types of response by treatment arm: measurable disease response; and PSA response.

III. To compare each of 7 time-to-event endpoints by treatment arm: duration of overall response (RD); duration of stable disease (SDD); time to treatment failure (TTF); time-to-progression (TTP); TTP in patients with bone metastases; progression-free survival (PFS); and overall survival (OS).

IV. To compare the rates of each type of toxicity by treatment arm. V. To compare the incidence rate of skeletal related events (SRE), and the time until SRE, separately by treatment arm.

VI. To compare the rates of circulating tumor cell (CTC) response by treatment arm.

VIII. To explore the molecular mechanisms within the androgen receptor pathway by determining the levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) expression, androgen metabolism enzymes; androgen receptor variants, and length of cytosine-adenine-guanine (CAG) repeats within the androgen receptor gene, and to associate them with the primary endpoint.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive enzalutamide orally (PO) once daily (QD) and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other Food and Drug Administration [FDA] approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity.

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

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (enzalutamide and LHRH analogue therapy)	Experimental	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: enzalutamide Procedure: orchiectomy Drug: leuprolide acetate Drug: goserelin acetate Other: laboratory biomarker analysis
Arm B (bicalutamide and LHRH analogue therapy)	Active Comparator	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: bicalutamide Procedure: orchiectomy Drug: leuprolide acetate Drug: goserelin acetate Other: laboratory biomarker analysis

Name	Type	Description	Arm Group Labels	Other Names
enzalutamide	Drug	Given PO	Arm A (enzalutamide and LHRH analogue therapy)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria	Number of Participants with PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria specifically at the 7 month time point. The binary endpoint (yes/no) will be summarized with its point estimate (an occurrence rate), and 2-sided Wilson type 95% confidence interval (CI). PSA response rates will be compared by treatment arm in a stratified logistic regression model.	Month 7

Secondary Outcomes

Measure	Description	Time Frame
Achievement of Measurable Disease Response	The number of participants with Measurable disease response per RECIST v1.1.	Up to 2 years
Achievement of PSA Response Assessed Using PCWG2 Criteria

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy. [Late induction permitted within 3 months of starting LHRH analogue therapy or antiandrogen]
All patients who have not initiated hormone therapy (Early induction patients) must have elevated PSA ≥ 4 ng/ml within 28 days prior to registration. For late induction registrations, PSA must be ≥ 4 ng/ml prior to start of androgen deprivation therapy; either antiandrogen or LHRH analogue or GNRH antagonist .If patients are on antiandrogen, this will need to be discontinued for at least 7 days prior to registration.
Patients with a history of prior neoadjuvant or adjuvant hormone therapy are eligible provided they have received twenty four or less months of hormone treatment (single or combination treatment, excluding orchiectomy). Both therapies (neoadjuvant/adjuvant hormone therapy) must have been discontinued at least 6 months prior to registration. This is intended to exclude patients who might have been rendered indirectly androgen insensitive.
There must be no plans to receive concomitant chemotherapy, biological response modifiers, radiation therapy or hormonal therapy. Concomitant radiation therapy is allowed for the palliation of severe pain/neuropathic compression. Prior or concomitant use of megestrol acetate for the treatment of hot flashes is allowed.
Patients must have a performance status of 0 - 2 by Zubrod Criteria.
Patients must have recovered from any major infections and/or surgical procedures and,in the opinion of the investigator, not have significant active medical illness precluding protocol treatment or survival.
No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, superficial or in situ cancer of the bladder. For an invasive cancer the patients should be disease free for at least 3 years prior to enrollment on study.
For all patients a bone scan must be performed within 60 days prior to registration for tumor assessment. CT scans (abdomen and pelvis) and chest x-ray are optional, but must be repeated if used for disease assessment. For late induction registrations, tumor assessment imaging showing metastatic disease must be available prior to start of androgen deprivation therapy.
Age 18 or older and willing and able to provide informed consent.
Willingness to swallow pills and no medical condition that would interfere with this.
Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Patients are also required to use a condom if having sex with a pregnant woman.
Patient should agree to a tumor tissue biopsy prior to protocol enrollment. Post therapy biopsy is optional.
Patients who are being treated with a GNRH antagonist should be willing to switch to a LHRH analogue after registration.
Patients must have one of the following a) Low volume disease (defined as no visceral metastases and < 4 bone metastases) or b) are not candidates for docetaxel based chemotherapy or 3) refused docetaxel chemotherapy

Exclusion Criteria:

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of Day 1 visit;
Known or suspected brain metastasis or active leptomeningeal disease;
Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
Absolute neutrophil count < 1,000/μL, or platelet count < 50,000/μL, or hemoglobin<8 g/dL) at the Screening visit.
Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal
Creatinine > 177 μmol/L (2 mg/dL)
Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure (NYHA) class 3 or 4 in the past, unless screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is greater or equal to 45%; History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes); History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit; Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG; Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg
Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
Treatment with concurrent 5-α reductase inhibitors (finasteride, dutasteride), estrogens, and/or cyproterone
Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumor activity within 4 weeks of enrollment (Day 1 visit);
History of prostate cancer progression on ketoconazole;
Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or agents that block the androgen receptor (e.g.,ARN-509)
Previous enzalutamide therapy;
Use of an investigational agent within 2 weeks of enrollment (Day 1 visit);
Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of replacement steroids or > equivalent of 10 mg of prednisone per day within 4 weeks of enrollment (Day 1 visit);
Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.
Prior chemotherapy for metastatic disease.
>30 days of antiandrogen therapy monotherapy without androgen deprivation therapy.
Life expectancy of 6 months or less.

Contacts/Locations Module

Name	Affiliation	Role
Elisabeth Heath, M.D.	Barbara Ann Karmanos Cancer Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
Barbara Ann Karmanos Cancer Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33496795	Derived	Vaishampayan UN, Heilbrun LK, Monk P 3rd, Tejwani S, Sonpavde G, Hwang C, Smith D, Jasti P, Dobson K, Dickow B, Heath EI, Semaan L, Cher ML, Fontana JA, Chinni S. Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2034633. doi: 10.1001/jamanetworkopen.2020.34633.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 20, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

selective androgen receptor modulator MDV3100

Will be summarized with point estimates (occurrence rates), and 2-sided Wilson type 95% CIs.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
BG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00036 BG00135 BG00271

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00066(54 to 86) BG00163(46 to 84) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00036 BG00135 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria

Number of Participants with PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria specifically at the 7 month time point. The binary endpoint (yes/no) will be summarized with its point estimate (an occurrence rate), and 2-sided Wilson type 95% confidence interval (CI). PSA response rates will be compared by treatment arm in a stratified logistic regression model.

Those patients who reached month 7 and had a blood sample tested for PSA at month 7.

Posted

Count of Participants

Participants

Month 7

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Units	Counts
Participants	OG00031 OG00124

Title

Denominators

Categories

Title	Measurements
	OG00029 OG00116

Secondary

Achievement of Measurable Disease Response

The number of participants with Measurable disease response per RECIST v1.1.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Achievement of PSA Response Assessed Using PCWG2 Criteria

Will be summarized with point estimates (occurrence rates), and 2-sided Wilson type 95% CIs.

Those patients who reached month 7 of treatment and had a blood sample tested for PSA at any time at or past month 7.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

The Percentage of Patients Responding

Point estimates will be calculated and CI estimates will be derived from the Wilcoxon method using STATA software.

Posted

Number

90% Confidence Interval

percentage of response at 6 months

6 months

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Time to Treatment Failure

Time to Treatment Failure from date of first treatment to date off treatment or date patient is taken off study for any reason. TTF will be estimated with standard K-M methodology. Point and CI estimates of the median and various time point-specific rates will be derived from the K-M life table.

Posted

Median

95% Confidence Interval

months

Assessed up to 6 years.

ID	Title	Description
OG000	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Percentage of Patients Progression Free at One Year

Percentage of patients progression free at one year using the Kaplan-Meier method.

Posted

Number

95% Confidence Interval

% participants not progressed at 1 year

assessed at 1 year

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Percentage of Patients With Bone Metastases Progression Free at Six Months

Percentage of patients with bone metastases Progression free at six months using the Kaplan-Meier method.

Patients with bone lesions at baseline.

Posted

Number

95% Confidence Interval

percentage not progressed at 6 months

assessed at six months

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Percentage of Patients Progression-free at 6 Months

Will be estimated with standard K-M methodology. Point and CI estimates of the six-month rate will be derived from the K-M life table.

Posted

Number

95% Confidence Interval

percentage progression-free at 6 months

From registration to PSA progression defined by PCWG II criteria or measurable disease by RECIST 1.1, assessed at 6 months

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

Overall Survival at 2 Years

Overall Survival will be measured from date of registration to death or last follow up. OS will be estimated with standard K-M methodology. Point and CI estimates of the 2-year rate will derived from the K-M life table.

Posted

Number

95% Confidence Interval

percentage alive at 2 years

Assessed at 2 years

ID	Title	Description
OG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Secondary

The Number of Participants With a CTC Response

Will be summarized with point estimates (occurrence rates). A CTC response is defined as any level of CTC < 5 that is maintained or any level of CTC that is reduced from baseline.

Patients with sufficient blood sample to test for CTC at baseline and post-treatment.

Posted

Count of Participants

Participants

Up to month 1

ID	Title	Description
OG000	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies
OG001	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (Enzalutamide and LHRH Analogue Therapy)	Patients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. enzalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies	8	36	17	36	33	36
EG001	Arm B (Bicalutamide and LHRH Analogue Therapy)	Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. bicalutamide: Given PO orchiectomy: Undergo orchiectomy or receive LHRH analogue therapy leuprolide acetate: Undergo orchiectomy or receive LHRH analogue therapy goserelin acetate: Undergo orchiectomy or receive LHRH analogue therapy laboratory biomarker analysis: Correlative studies	18	35	16	35	33	35

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaphylaxis	Immune system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Anemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0013 events1 affected35 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Blood bilirubin increased	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Cardiac arrest	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Cardiac disorders - Other, specify	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Chest pain - cardiac	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Dehydration	General disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Depression	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Diarrhea	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Fall	General disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Fatigue	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0013 events2 affected35 at risk
Hematuria	Renal and urinary disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected35 at risk
Hot flashes	Endocrine disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Hyperglycemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected35 at risk
Hypertension	Vascular disorders	Non-systematic Assessment	EG0006 events5 affected36 at risk EG0019 events6 affected35 at risk
Hypertriglyceridemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Hypokalemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Hypomagnesemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
INR increased	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Injection site reaction	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Investigations - Other, specify	Investigations	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Lymphocyte count decreased	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Myocardial infarction	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0012 events2 affected35 at risk
Neutrophil count decreased	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Non-cardiac chest pain	General disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Pain	General disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Renal and urinary disorders - Other, specify	Renal and urinary disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Restrictive cardiomyopathy	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Suicidal ideation	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Syncope	Vascular disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected35 at risk
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Urinary tract infection	Renal and urinary disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected35 at risk
Vascular disorders - Other, specify	Vascular disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk
Weight gain	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Weight loss	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected35 at risk
Wound infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected35 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0015 events4 affected35 at risk
Anorexia	General disorders	Non-systematic Assessment	EG0009 events7 affected36 at risk EG0012 events2 affected35 at risk
Anxiety	Psychiatric disorders	Non-systematic Assessment	EG0004 events4 affected36 at risk EG0011 events1 affected35 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0012 events2 affected35 at risk
Arthritis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0013 events3 affected35 at risk
Aspartate aminotransferase increased	Investigations	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0014 events2 affected35 at risk
Back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0005 events4 affected36 at risk EG0016 events6 affected35 at risk
Blurred vision	Eye disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected35 at risk
Bruising	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected35 at risk
Chills	General disorders	Non-systematic Assessment	EG0002 events1 affected36 at risk EG0012 events2 affected35 at risk
Confusion	Psychiatric disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected35 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0008 events7 affected36 at risk EG0013 events3 affected35 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected35 at risk
Dehydration	Metabolism and nutrition disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0012 events2 affected35 at risk
Depression	Psychiatric disorders	Non-systematic Assessment	EG0005 events5 affected36 at risk EG0011 events1 affected35 at risk
Diarrhea	Gastrointestinal disorders	Non-systematic Assessment	EG00012 events9 affected36 at risk EG0011 events1 affected35 at risk
Dizziness	Nervous system disorders	Non-systematic Assessment	EG00014 events8 affected36 at risk EG0013 events3 affected35 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00010 events8 affected36 at risk EG0011 events1 affected35 at risk
Fall	General disorders	Non-systematic Assessment	EG0004 events3 affected36 at risk EG0011 events1 affected35 at risk
Fatigue	General disorders	Non-systematic Assessment	EG00022 events19 affected36 at risk EG00111 events10 affected35 at risk
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0012 events2 affected35 at risk
General disorders and administration site conditions - Other, specify	General disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0014 events3 affected35 at risk
Headache	Nervous system disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0018 events6 affected35 at risk
Hot flashes	Vascular disorders	Non-systematic Assessment	EG00028 events25 affected36 at risk EG00123 events20 affected35 at risk
Hypertension	Vascular disorders	Non-systematic Assessment	EG0009 events7 affected36 at risk EG0015 events3 affected35 at risk
Hypotension	Vascular disorders	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0011 events1 affected35 at risk
Insomnia	Psychiatric disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0014 events4 affected35 at risk
Memory impairment	Nervous system disorders	Non-systematic Assessment	EG0006 events6 affected36 at risk EG0011 events1 affected35 at risk
Musculoskeletal and connective tissue disorder - Other, specify	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG00012 events7 affected36 at risk EG0017 events4 affected35 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0012 events1 affected35 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0006 events6 affected36 at risk EG0012 events2 affected35 at risk
Nervous system disorders - Other, specify	Nervous system disorders	Non-systematic Assessment	EG0007 events5 affected36 at risk EG0011 events1 affected35 at risk
Pain	General disorders	Non-systematic Assessment	EG00018 events13 affected36 at risk EG00113 events6 affected35 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0006 events6 affected36 at risk EG0016 events4 affected35 at risk
Peripheral sensory neuropathy	Nervous system disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected35 at risk
Psychiatric disorders - Other, specify	Psychiatric disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0014 events3 affected35 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0013 events3 affected35 at risk
Renal and urinary disorders - Other, specify	Renal and urinary disorders	Non-systematic Assessment	EG00010 events7 affected36 at risk EG0011 events1 affected35 at risk
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0008 events6 affected36 at risk EG0011 events1 affected35 at risk
Skin infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0015 events3 affected35 at risk
Tinnitus	Ear and labyrinth disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected35 at risk
Urinary frequency	Renal and urinary disorders	Non-systematic Assessment	EG0005 events4 affected36 at risk EG0017 events6 affected35 at risk
Urinary incontinence	Renal and urinary disorders	Non-systematic Assessment	EG0001 events1 affected36 at risk EG0012 events2 affected35 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0004 events3 affected36 at risk EG0010 events0 affected35 at risk
Weight gain	General disorders	Non-systematic Assessment	EG0006 events3 affected36 at risk EG0019 events4 affected35 at risk
Weight loss	Investigations	Non-systematic Assessment	EG0007 events5 affected36 at risk EG0012 events2 affected35 at risk
Edema limbs	General disorders	Non-systematic Assessment	EG0003 events2 affected36 at risk EG0015 events4 affected35 at risk
Erectile dysfunction	Reproductive system and breast disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0017 events5 affected35 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0005 events5 affected36 at risk EG0016 events3 affected35 at risk

ID	Term
D011471	Prostatic Neoplasms

Ancestor Terms

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
C540278	enzalutamide
C053541	bicalutamide
D009919	Orchiectomy
D016729	Leuprolide
D017273	Goserelin

Ancestor Terms

ID	Term
D002369	Castration
D013507	Endocrine Surgical Procedures
D013514	Surgical Procedures, Operative
D013519	Urogenital Surgical Procedures
D013521	Urologic Surgical Procedures, Male
D013520	Urologic Surgical Procedures
D007987	Gonadotropin-Releasing Hormone
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins

Units	Counts
Participants	OG00036 OG00135

Units	Counts
Participants	OG00036 OG00135

Units	Counts
Participants	OG00036 OG00135