Trial Outcomes & Findings for LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer (NCT NCT02058706)

NCT ID: NCT02058706

Last Updated: 2023-05-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

71 participants

Primary outcome timeframe

Month 7

Results posted on

2023-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	35	36
Overall Study COMPLETED	35	36
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	17 Participants n=7 Participants	39 Participants n=5 Participants
Age, Continuous	66 years n=5 Participants	63 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	35 participants n=7 Participants	71 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 7

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=31 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=24 Participants 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
Number of Participants With PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria	29 Participants	16 Participants

SECONDARY outcome

Timeframe: Up to 2 years

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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
Achievement of Measurable Disease Response	17 Participants	17 Participants

SECONDARY outcome

Timeframe: Up to 2 years

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

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=32 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=26 Participants 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
Achievement of PSA Response Assessed Using PCWG2 Criteria	30 Participants	17 Participants

SECONDARY outcome

Timeframe: 6 months

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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
The Percentage of Patients Responding	86 percentage of response at 6 months Interval 62.0 to 95.0	79 percentage of response at 6 months Interval 48.0 to 92.0

SECONDARY outcome

Timeframe: Assessed up to 6 years.

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.

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=35 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=36 Participants 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
Time to Treatment Failure	8.2 months Interval 5.7 to 11.4	20.6 months Interval 6.9 to 42.3

SECONDARY outcome

Timeframe: assessed at 1 year

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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
Percentage of Patients Progression Free at One Year	84 % participants not progressed at 1 year Interval 57.0 to 95.0	34 % participants not progressed at 1 year Interval 15.0 to 58.0

SECONDARY outcome

Timeframe: assessed at six months

Population: Patients with bone lesions at baseline.

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

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=31 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=28 Participants 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
Percentage of Patients With Bone Metastases Progression Free at Six Months	91 percentage not progressed at 6 months Interval 63.0 to 98.0	33 percentage not progressed at 6 months Interval 14.0 to 54.0

SECONDARY outcome

Timeframe: From registration to PSA progression defined by PCWG II criteria or measurable disease by RECIST 1.1, assessed 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.

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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
Percentage of Patients Progression-free at 6 Months	92 percentage progression-free at 6 months Interval 66.0 to 98.0	45 percentage progression-free at 6 months Interval 25.0 to 64.0

SECONDARY outcome

Timeframe: Assessed 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.

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 Participants 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
Overall Survival at 2 Years	82 percentage alive at 2 years Interval 63.0 to 92.0	54 percentage alive at 2 years Interval 34.0 to 70.0

SECONDARY outcome

Timeframe: Up to month 1

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

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.

Outcome measures

Outcome measures
Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=25 Participants 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 B (Bicalutamide and LHRH Analogue Therapy) n=26 Participants 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
The Number of Participants With a CTC Response	17 Participants	22 Participants

Adverse Events

Arm A (Enzalutamide and LHRH Analogue Therapy)

Serious events: 17 serious events

Other events: 33 other events

Deaths: 8 deaths

Arm B (Bicalutamide and LHRH Analogue Therapy)

Serious events: 16 serious events

Other events: 33 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Elisabeth Heath

Karmanos Cancer Institute

Phone: 313.576.8734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 participants at risk 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 participants at risk 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
Immune system disorders Anaphylaxis	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Anemia	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Blood bilirubin increased	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Cardiac disorders Cardiac arrest	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Cardiac disorders Cardiac disorders - Other, specify	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Cardiac disorders Chest pain - cardiac	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
General disorders Dehydration	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Depression	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Diarrhea	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
General disorders Fall	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Metabolism and nutrition disorders Fatigue	0.00% 0/36 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Hematuria	0.00% 0/36 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Endocrine disorders Hot flashes	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Hyperglycemia	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Vascular disorders Hypertension	13.9% 5/36 • Number of events 6 • Adverse Events were assessed up to 2 years.	17.1% 6/35 • Number of events 9 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Hypertriglyceridemia	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Hypokalemia	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Hypomagnesemia	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders INR increased	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Skin and subcutaneous tissue disorders Injection site reaction	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Investigations Investigations - Other, specify	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Lymphocyte count decreased	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Cardiac disorders Myocardial infarction	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Nausea	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Blood and lymphatic system disorders Neutrophil count decreased	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
General disorders Non-cardiac chest pain	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
General disorders Pain	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Cardiac disorders Restrictive cardiomyopathy	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Suicidal ideation	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Vascular disorders Syncope	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Urinary tract infection	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Vascular disorders Vascular disorders - Other, specify	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Vomiting	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Metabolism and nutrition disorders Weight gain	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Metabolism and nutrition disorders Weight loss	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Infections and infestations Wound infection	0.00% 0/36 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.

Measure	Arm A (Enzalutamide and LHRH Analogue Therapy) n=36 participants at risk 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 B (Bicalutamide and LHRH Analogue Therapy) n=35 participants at risk 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
Gastrointestinal disorders Abdominal pain	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 5 • Adverse Events were assessed up to 2 years.
General disorders Anorexia	19.4% 7/36 • Number of events 9 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Anxiety	11.1% 4/36 • Number of events 4 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Arthritis	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Investigations Aspartate aminotransferase increased	0.00% 0/36 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 4 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Back pain	11.1% 4/36 • Number of events 5 • Adverse Events were assessed up to 2 years.	17.1% 6/35 • Number of events 6 • Adverse Events were assessed up to 2 years.
Eye disorders Blurred vision	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Injury, poisoning and procedural complications Bruising	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
General disorders Chills	2.8% 1/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Confusion	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Constipation	19.4% 7/36 • Number of events 8 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Metabolism and nutrition disorders Dehydration	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Depression	13.9% 5/36 • Number of events 5 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Diarrhea	25.0% 9/36 • Number of events 12 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Nervous system disorders Dizziness	22.2% 8/36 • Number of events 14 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	22.2% 8/36 • Number of events 10 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
General disorders Fall	8.3% 3/36 • Number of events 4 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
General disorders Fatigue	52.8% 19/36 • Number of events 22 • Adverse Events were assessed up to 2 years.	28.6% 10/35 • Number of events 11 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
General disorders General disorders and administration site conditions - Other, specify	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 4 • Adverse Events were assessed up to 2 years.
Nervous system disorders Headache	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	17.1% 6/35 • Number of events 8 • Adverse Events were assessed up to 2 years.
Vascular disorders Hot flashes	69.4% 25/36 • Number of events 28 • Adverse Events were assessed up to 2 years.	57.1% 20/35 • Number of events 23 • Adverse Events were assessed up to 2 years.
Vascular disorders Hypertension	19.4% 7/36 • Number of events 9 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 5 • Adverse Events were assessed up to 2 years.
Vascular disorders Hypotension	5.6% 2/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Insomnia	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 4 • Adverse Events were assessed up to 2 years.
Nervous system disorders Memory impairment	16.7% 6/36 • Number of events 6 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	19.4% 7/36 • Number of events 12 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 7 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Nausea	16.7% 6/36 • Number of events 6 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Nervous system disorders Nervous system disorders - Other, specify	13.9% 5/36 • Number of events 7 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
General disorders Pain	36.1% 13/36 • Number of events 18 • Adverse Events were assessed up to 2 years.	17.1% 6/35 • Number of events 13 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 6/36 • Number of events 6 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 6 • Adverse Events were assessed up to 2 years.
Nervous system disorders Peripheral sensory neuropathy	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Psychiatric disorders Psychiatric disorders - Other, specify	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 4 • Adverse Events were assessed up to 2 years.
Skin and subcutaneous tissue disorders Rash acneiform	8.3% 3/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 3 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Renal and urinary disorders - Other, specify	19.4% 7/36 • Number of events 10 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	16.7% 6/36 • Number of events 8 • Adverse Events were assessed up to 2 years.	2.9% 1/35 • Number of events 1 • Adverse Events were assessed up to 2 years.
Infections and infestations Skin infection	0.00% 0/36 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 5 • Adverse Events were assessed up to 2 years.
Ear and labyrinth disorders Tinnitus	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Urinary frequency	11.1% 4/36 • Number of events 5 • Adverse Events were assessed up to 2 years.	17.1% 6/35 • Number of events 7 • Adverse Events were assessed up to 2 years.
Renal and urinary disorders Urinary incontinence	2.8% 1/36 • Number of events 1 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
Gastrointestinal disorders Vomiting	8.3% 3/36 • Number of events 4 • Adverse Events were assessed up to 2 years.	0.00% 0/35 • Adverse Events were assessed up to 2 years.
General disorders Weight gain	8.3% 3/36 • Number of events 6 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 9 • Adverse Events were assessed up to 2 years.
Investigations Weight loss	13.9% 5/36 • Number of events 7 • Adverse Events were assessed up to 2 years.	5.7% 2/35 • Number of events 2 • Adverse Events were assessed up to 2 years.
General disorders Edema limbs	5.6% 2/36 • Number of events 3 • Adverse Events were assessed up to 2 years.	11.4% 4/35 • Number of events 5 • Adverse Events were assessed up to 2 years.
Reproductive system and breast disorders Erectile dysfunction	5.6% 2/36 • Number of events 2 • Adverse Events were assessed up to 2 years.	14.3% 5/35 • Number of events 7 • Adverse Events were assessed up to 2 years.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	13.9% 5/36 • Number of events 5 • Adverse Events were assessed up to 2 years.	8.6% 3/35 • Number of events 6 • Adverse Events were assessed up to 2 years.