Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Hormones

Leuprolide

Prolactin Release-Inhibiting Factors

Antineoplastic Agents, Hormonal

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.

Enzalutamide

A total dose of 45 Gy in 25 fractions of 1.8 Gy each.

Intensity-Modulated Radiation Therapy

Hao Nguyen, MD

This phase II trial studies the safety of giving enzalutamide with leuprolide acetate before and after radiation therapy and to see how well it works in treating patients with prostate cancer that is at high risk of returning. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Most types of prostate cancer also need testosterone to grow and spread. After radiation therapy, patients often receive treatments to reduce testosterone to prevent the cancer from returning. Leuprolide acetate works by reducing the amount of testosterone that the body makes. Enzalutamide is a stronger treatment that may block testosterone from reaching cancer cells. Adding enzalutamide to treatment with leuprolide acetate after radiation therapy may help prevent high-risk prostate cancer from returning and improve patient survival.

PRIMARY OBJECTIVES:

I. To determine the feasibility and safety of the combination of enzalutamide and leuprolide acetate (leuprolide) in patients undergoing definitive radiation therapy for high-risk prostate cancer or with pelvic nodal involvement.

II. To determine the prostate-specific antigen (PSA) complete response rate with the combination of enzalutamide and leuprolide (PSA-complete response (CR) as determined by PSA nadir =\< 0.3) in patients undergoing radiation therapy for high-risk prostate cancer or pelvic nodal involvement.

SECONDARY OBJECTIVES:

I. To determine time to biochemical failure as determined by the American Society for Radiation Oncology (ASTRO) Phoenix definition of nadir + 2 ng/mL, local progression, regional progression, and distant metastases.

II. To determine time to clinical progression free survival III. To assess changes in PSA nadir and PSA and testosterone levels. IV. To assess changes in hemoglobin A1c (HbA1c), fasting glucose, fasting insulin and fasting lipid and cholesterol levels.

V. To document changes in quality of life outcomes.

EXPLORATORY OBJECTIVES:

I. To identify potential mutations and changes gene copy number associated with enzalutamide resistance in patients with high risk prostate cancer.

II. To identify gene expression patterns, splice variants, and gene signatures associated with enzalutamide treatment and enzalutamide resistance in patients with high risk prostate cancer.

III. To identify changes in the immune response with enzalutamide treatment.

OUTLINE:

Patients receive enzalutamide orally (PO) once daily (QD) and leuprolide acetate intramuscularly (IM) every 1, 3, 4, or 6 months for 24 months. Patients also undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for 5 weeks beginning at week 8, followed by optional brachytherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 weeks, 3-4 months, 6, 12, 18, 24, and 36 months.

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

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

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

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.

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.

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.

Local failure was defined as the time from the start of treatment to a biopsy confirmed disease recurrence.

The number of participants with confirmed regional or distant metastases at 24 and 36 months will be reported.

Defined as the time from the start of study treatment to confirmed regional or distant metastases

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.

Changes in fasting glucose levels results will be assessed during treatment and the overall median change in fasting glucose levels will be reported.

Changes in fasting insulin levels will be assessed during treatment and the overall median change in fasting insulin levels will be reported.

Changes in fasting lipid levels will be assessed during treatment and the overall median change in fasting lipid levels will be reported.

Changes in total cholesterol levels will be assessed during treatment and the overall median change in total cholesterol levels will be reported.

Changes in fasting HDL levels will be assessed during treatment and the overall median change in fasting HDL will be reported.

Changes in fasting LDL levels will be assessed during treatment and the overall median change in fasting LDL will be reported.

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.

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.

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.

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.

National Comprehensive Cancer Network

University of California, San Francisco

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;

Combination Therapy: Enzalutamide and Leuprolide

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Score of 0

Score of 1

Score of 2

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.

Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status

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

Dr. Hao Nguyen

Percentage of Participants With Acute Treatment-related Toxicity

Percentage of Participants With Late Treatment-related Toxicity

Proportion of Patients Achieving a Prostate Specific Antigen-Complete Response (PSA-CR)

Only participants experiencing biochemical failure are reported

Median Time to Biochemical Failure

Median Time to Local Failure

Month 24

Month 36

Number of Participants With Regional or Distant Metastases Over Time

Median Time to Clinical Progression

Overall Median Change in Hemoglobin A1c (HbA1c) Levels During Treatment

Overall Median Change in Fasting Glucose Levels During Treatment

Data for fasting insulin was not collected

Overall Median Change in Fasting Insulin Levels During Treatment

Overall Median Change in Lipid Levels During Treatment

Overall Median Change in Total Cholesterol Levels During Treatment

Overall Median Change in High-Density Lipoprotein (HDL) Cholesterol Levels During Treatment

Overall Median Change in Low-Density Lipoprotein (LDL) Cholesterol Levels During Treatment

Urinary incontinence

Urinary Irritative/Obstructive

Bowel

Sexual

Hormonal

Two participants did not complete the questionnaire

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trial of Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer	NCT02508636	Prostatic Neopl... Pelvic Nodal	Enzalutamide Leuprolide Intensity-Modul...	18 Years -	University of California, San Francisco
Trial of Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer	NCT02508636	Prostatic Neopl... Pelvic Nodal	Enzalutamide Leuprolide Intensity-Modul...	18 Years -	University of California, San Francisco

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