Trial of Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02508636
• Recruitment Status: Terminated
• First Posted: July 27, 2015
• Results First Posted: October 12, 2021
• Last Update Posted: October 12, 2021
• Sponsor: University of California, San Francisco
• Collaborator: National Comprehensive Cancer Network
• Information provided by (Responsible Party): University of California, San Francisco

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Prostatic Neoplasms; Pelvic Nodal
• Interventions: Drug: Enzalutamide; Drug: Leuprolide; Radiation: Intensity-Modulated Radiation Therapy
• Enrollment: 11

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Period Title: Overall Study
Started	11
Completed	11
Not Completed	0

Baseline Characteristics

Arm/Group Title		Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description		Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Baseline Participants		11
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	11 participants
		69.0; (50 to 85)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Female	0 0.0%
	Male	11 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	11 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 9.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 18.2%
	White	6 54.5%
	More than one race	0 0.0%
	Unknown or Not Reported	2 18.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	11 participants
		11
Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	11 participants
Score of 0		9
Score of 1		2
Score of 2		0
		[1] Measure Description: The ECOG Scale of Performance Status describes a patient's level of functioning in terms of their ability to care for themselves, their daily activity, and physical ability (walking, working, etc.). The scale/grade ranges from 0 to 5 with lower scores indicating a greater level of functioning.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Acute Treatment-related Toxicity
Description	Percentage of participants with acute, treatment-related toxicity defined as <=90 days within the completion of radiotherapy, for any treatment-related grade 3 or higher adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	From start of treatment to 90 days after completion of radiotherapy, approximately 6 months total

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: percentage of participants
	36.36

2. Primary Outcome

Title	Percentage of Participants With Late Treatment-related Toxicity
Description	Percentage of participants with late, treatment-related, toxicity is defined as any toxicity occurring >= 90 days from completion of radiotherapy for any grade 3 or higher treatment-related adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame	From 90 days after completion of radiotherapy until end of study, approximately 30 months total

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: percentage of participants
	27.27

3. Primary Outcome

Title	Proportion of Patients Achieving a Prostate Specific Antigen-Complete Response (PSA-CR)
Description	A PSA measurement will be obtained at 120-127 days after initiation of androgen deprivation therapy. The proportion of patients achieving a PSA-CR (PSA nadir <=0.3) at 120-127 days will be determined.
Time Frame	Up to 127 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: proportion of participants
	0.818

4. Secondary Outcome

Title	Median Time to Biochemical Failure
Description	Prostate-specific antigen (PSA) nadir >=2 ng/mL, also known as the Phoenix definition, is the definition most commonly used to establish biochemical failure (BF) after external beam radiotherapy for prostate cancer management. Time to biochemical failure is defined as the time from start of treatment to the time of change in PSA >=2 ng/mL from the nadir.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

Only participants experiencing biochemical failure are reported

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	1
Median (95% Confidence Interval); Unit of Measure: months
	36 [1]; (NA to NA)

[1]

Only 1 participant had biochemical failure at 36 months so there were not a sufficient number of events for a confidence interval to be computed

5. Secondary Outcome

Title	Median Time to Local Failure
Description	Local failure was defined as the time from the start of treatment to a biopsy confirmed disease recurrence.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

No participants displayed local failure at 36 months so there were not a sufficient number of events for a confidence interval to be computed

6. Secondary Outcome

Title	Number of Participants With Regional or Distant Metastases Over Time
Description	The number of participants with confirmed regional or distant metastases at 24 and 36 months will be reported.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Measure Type: Count of Participants; Unit of Measure: Participants
Month 24	0 0.0%
Month 36	0 0.0%

7. Secondary Outcome

Title	Median Time to Clinical Progression
Description	Defined as the time from the start of study treatment to confirmed regional or distant metastases
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

No participants displayed clinical progression so there was an insufficient number of events to calculate median and confidence interval

8. Secondary Outcome

Title	Overall Median Change in Hemoglobin A1c (HbA1c) Levels During Treatment
Description	HbA1C test results are reported as a percentage. The higher the percentage, the higher your blood sugar levels over the past two to three months. Changes in HbA1c results will be assessed during treatment and the overall median change in HbA1c will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: percentage
	0.2; (-1.1 to 1.5)

9. Secondary Outcome

Title	Overall Median Change in Fasting Glucose Levels During Treatment
Description	Changes in fasting glucose levels results will be assessed during treatment and the overall median change in fasting glucose levels will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: mg/dL
	-2.7; (-20 to 19)

10. Secondary Outcome

Title	Overall Median Change in Fasting Insulin Levels During Treatment
Description	Changes in fasting insulin levels will be assessed during treatment and the overall median change in fasting insulin levels will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Data for fasting insulin was not collected

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

11. Secondary Outcome

Title	Overall Median Change in Lipid Levels During Treatment
Description	Changes in fasting lipid levels will be assessed during treatment and the overall median change in fasting lipid levels will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: mg/dL
	0; (-101 to 86)

12. Secondary Outcome

Title	Overall Median Change in Total Cholesterol Levels During Treatment
Description	Changes in total cholesterol levels will be assessed during treatment and the overall median change in total cholesterol levels will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: mg/dL
	12; (-270 to 86)

13. Secondary Outcome

Title	Overall Median Change in High-Density Lipoprotein (HDL) Cholesterol Levels During Treatment
Description	Changes in fasting HDL levels will be assessed during treatment and the overall median change in fasting HDL will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: mg/dL
	12; (-18 to 105)

14. Secondary Outcome

Title	Overall Median Change in Low-Density Lipoprotein (LDL) Cholesterol Levels During Treatment
Description	Changes in fasting LDL levels will be assessed during treatment and the overall median change in fasting LDL will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	11
Median (Full Range); Unit of Measure: mg/dL
	0; (-201 to 81)

15. Secondary Outcome

Title	Overall Median Change in Score on the Expanded Prostate Cancer Index Composite (EPIC) During Treatment
Description	The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment and assesses the disease-specific aspects of prostate cancer and its therapies and comprises four summary domains (Urinary, Bowel, Sexual and Hormonal). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Changes in EPIC scores will be assessed during treatment and the overall median change in scores will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Two participants did not complete the questionnaire

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	9
Median (Full Range); Unit of Measure: score on a scale
Urinary incontinence	6.25; (-20.8 to 25)
Urinary Irritative/Obstructive	6.25; (-6.25 to 25)
Bowel	0; (-20.8 to 4.2)
Sexual	-44.4; (-56.9 to 0)
Hormonal	-20; (-75 to 5)

16. Secondary Outcome

Title	Overall Median Change in Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Scores During Treatment
Description	A PROMIS score of 50 is the average (or mean) score for a specific, relevant group of people under investigation. That group is the reference population. The PROMIS measures the responses use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. A score of 40 is one SD lower than the mean of the reference population and a score of 60 is one SD higher than the mean of the reference population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue). Changes in the PROMIS fatigue scores will be assessed during treatment and the overall median change in scores will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Two participants did not complete the questionnaire

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	9
Median (Full Range); Unit of Measure: score on a scale
	0; (-9.6 to 21.5)

17. Secondary Outcome

Title	Overall Median Change in EuroQol Group Five Dimensional Questionnaire (EQ-5D) During Treatment
Description	EQ-5D is a standardized instrument for measuring generic health status. The health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The respondents self-rate their level of severity for each dimension by selecting one of the following responses: no problems (0), slight problems (1), mild problems (2), moderate problems (3), or severe problems (4) with a particular dimension. Lower scores indicate less issues/problems with that particular health dimension. Changes in the EQ-5D scores will be assessed during treatment and the overall median change in scores will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Two participants did not complete the questionnaire

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	9
Median (Full Range); Unit of Measure: score on a scale
Mobility	0; (0 to 1)
Self-Care	0; (0 to 1)
Usual Activities	0; (0 to 1)
Pain/Discomfort	0; (0 to 2)
Anxiety/Depression	0; (0 to 1)

18. Secondary Outcome

Title	Overall Median Change in EuroQol Group Visual Analog Scale (EQ-VAS) During Treatment
Description	The EQ-VAS records the patient's self-rated health on a vertical visual analogue scale, similar to a ruler, where the endpoints are labelled with 100='The best health you can imagine' on one end and 0='The worst health you can imagine' on the other, with 50 being the midpoint and participants mark an X on the scale to indicate how their health is on the day of the visit. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. Changes in the EQ-VAS scores will be assessed during treatment and the overall median change in scores will be reported.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Two participants did not complete the questionnaire

Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description:	Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
Overall Number of Participants Analyzed	9
Median (Full Range); Unit of Measure: score on a scale
	72; (-2 to 81)

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Combination Therapy: Enzalutamide and Leuprolide
Arm/Group Description	Enzalutamide: 160 mg (for 40 mg capsules) per day; Oral administration to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months. Leuprolide: any duration formulation: single 7.5mg intramuscular injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months;
All-Cause Mortality
	Combination Therapy: Enzalutamide and Leuprolide
	Affected / at Risk (%)
Total	0/11 (0.00%)
Serious Adverse Events
	Combination Therapy: Enzalutamide and Leuprolide
	Affected / at Risk (%)	# Events
Total	1/11 (9.09%)
Nervous system disorders
Seizure † 1	1/11 (9.09%)	1
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Combination Therapy: Enzalutamide and Leuprolide
	Affected / at Risk (%)	# Events
Total	11/11 (100.00%)
Gastrointestinal disorders
Diarrhea † 1	3/11 (27.27%)	5
Constipation † 1	1/11 (9.09%)	1
Gastroesophageal reflux disease † 1	1/11 (9.09%)	1
Proctitis † 1	1/11 (9.09%)	1
General disorders
Fatigue † 1	2/11 (18.18%)	3
General disorders and administration site conditions - Other † 1	1/11 (9.09%)	1
Infections and infestations
Urinary tract infection † 1	1/11 (9.09%)	1
Investigations
Weight gain † 1	2/11 (18.18%)	2
Aspartate aminotransferase increased † 1	1/11 (9.09%)	1
Creatinine increased † 1	1/11 (9.09%)	1
Weight loss † 1	1/11 (9.09%)	1
Metabolism and nutrition disorders
Anorexia † 1	1/11 (9.09%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other † 1	2/11 (18.18%)	2
Myalgia † 1	1/11 (9.09%)	1
Nervous system disorders
Cognitive disturbance † 1	2/11 (18.18%)	2
Dysgeusia † 1	1/11 (9.09%)	1
Headache † 1	1/11 (9.09%)	1
Psychiatric disorders
Libido decreased † 1	1/11 (9.09%)	1
Renal and urinary disorders
Urinary frequency † 1	11/11 (100.00%)	40
Urinary urgency † 1	10/11 (90.91%)	15
Urinary retention † 1	4/11 (36.36%)	5
Urinary incontinence † 1	3/11 (27.27%)	4
Cystitis noninfective † 1	2/11 (18.18%)	2
Chronic kidney disease † 1	1/11 (9.09%)	1
Renal and urinary disorders - Other † 1	1/11 (9.09%)	2
Reproductive system and breast disorders
Erectile dysfunction † 1	9/11 (81.82%)	12
Reproductive system and breast disorders - Other † 1	1/11 (9.09%)	2
Skin and subcutaneous tissue disorders
Alopecia † 1	1/11 (9.09%)	1
Skin and subcutaneous tissue disorders - Other † 1	1/11 (9.09%)	1
Vascular disorders
Hot flashes † 1	11/11 (100.00%)	13
Lymphedema † 1	2/11 (18.18%)	2
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

The study closed earlier than expected which resulted in a low accrual

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Hao Nguyen
• Organization: University of California, San Francisco
• Phone: (415) 514-5541
• EMail: Hao.Nguyen@ucsf.edu

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02508636
• Other Study ID Numbers: 15558; NCI-2015-01757 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
• First Submitted: July 23, 2015
• First Posted: July 27, 2015
• Results First Submitted: August 3, 2021
• Results First Posted: October 12, 2021
• Last Update Posted: October 12, 2021