Enzalutamide and Hormone Therapy Before, During, and After Radiation for High Risk Localized Prostate Cancer

Study Overview
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Brief Summary
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The study is being done to find out whether combining two FDA approved drugs along with radiation therapy for the treatment of high risk localized prostate cancer is safe and well tolerated.

Detailed Description
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this pilot study will assess the safety and tolerability of combining enzalutamide with an gonadotropin-releasing hormone agonist (GnRH) and external beam radiation Correlative imaging and tissue biopsy analysis will be performed to assess the radiographic response to enzalutamide plus gonadotropin-releasing hormone agonist (GnRH) therapy as well as intratumoral androgen signaling

Official Title
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Phase 2 Study of Enzalutamide and GnRH Agonist Before, During and After Radiation Therapy in Treatment of Patients With High-risk Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide
* Drug: Leuprolide acetate
* Radiation: radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically proven adenocarcinoma of the prostate within 6 months of screening Eastern Cooperative Oncology Group(ECOG) score 0-2 adequate organ and and blood marrow function must be a candidate for long-term androgen deprivation in combination with external beam radiation for the treatment of high risk prostate cancer patient must permit a targeted prostate biopsy at the time of study initiation or at the beginning of radiation treatment men who are sexually active with female partners of child-bearing potential mush agree to use adequate contraception Exclusion Criteria: prior treatment with agents known to have endocrine effects on prostate cancer treatment with corticosteroids within 4 weeks of enrollment treatment with androgens within 6 months of enrollment may not be receiving any other investigational agents Prostate specific antigen greater than 160ng/dL history of malignancy( other than non-melanoma skin cancer) within 5 years uncontrolled intercurrent illness cardiovascular event within 6 months of enrollment seizure or seizure disorder history contraindications to MRI- pacemakers, clips, etc

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Enzalutamide, Leuprolide, radiation<br>Single arm Enzalutamide 160 mg daily for 6 months Leuprolide acetate 22.5mg every 3 months or 45mg every 6 months Radiation therapy as standard of care | Drug: Enzalutamide<br>* 160mg by mouth each day<br>* Other names: Xtandi;Drug: Leuprolide acetate<br>* 22.5 mg intramuscular every 3 months or 45mg intramuscular every 6 months<br>* Other names: Lupron;Radiation: radiation<br>* External beam radiation will be delivered as per standard radiation therapy protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as Measured by the Number of Patients With at Least One Adverse Event as Assess by NCI Common Terminology Criteria for Adverse Events (CTCAE) vs. 40 When Combining Enzalutamide With a GnRH and External Beam Radiation | Assessment will number of participants who experience adverse events greater than or equal to Grade 3, as defined by NCI Common terminology criteria for adverse events(CTCAE) v4.0 | 12 months following initiation of treatment with enzalutamide plus GnRH agonist | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | Fold change of Intra-tumoral Androgen Regulated Gene Expression (PSA, FKBP5, TMPRSS2, and NDRG1) will be measure at 12 months post therapy. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, enzalutamide, radiation, hormone therapy