A Study of Shorter Course Hormone Therapy and Radiation for High-risk Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find out whether combining a shorter than standard course of ADT with standard prostate brachytherapy and hypofractionated external beam radiation therapy is a safe and effective way to prevent high-risk prostate cancer from coming back and/or spreading to other parts of the body.

Official Title
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Phase II Trial of Short Course Androgen Deprivation, Hypofractionated Pelvic Radiation and a Brachytherapy Boost for NCCN High-Risk Prostate Cancer With Low-Intermediate Risk Decipher Genomic Score

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Androgen deprivation therapy (ADT)
* Radiation: Brachytherapy
* Radiation: Hypofractionated pelvic External beam radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically-proven diagnosis of prostate adenocarcinoma Clinical stage T3-4 or Gleason score 8-10 or PSA >20 ng/ml °If radiographic T3-T4 is the only high-risk factor, it must be consistent with or >90% probability of having T3-T4 disease determined by the reading radiologist. Decipher genomic score ≤0.6 Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization) Age ≥18 KPS ≥70 or ECOG 0-2 Estimated life expectancy >5 years Baseline prostate volume ≤90 cc Baseline IPSS ≤20 No contraindications to ADT, brachytherapy, or pelvic external beam radiation therapy as determined by the treating radiation oncologist per standard practice Patients who have already started ADT consisting of bicalutamide 50 mg PO daily with leuprolide or an equivalent GnRH analogue are eligible if given for ≤ 60 days prior to registration Exclusion Criteria: Regional lymph node or metastatic disease Prior pelvic radiation Prior prostate surgery (including TURP or cryosurgery) Prior history of inflammatory bowel disease Unable to undergo anesthesia or brachytherapy Active second malignancy or past history of malignancies diagnosed within the last 2 years that requires active therapy and/or in remission, with the exception of resected non-melanoma skin cancers, non-muscle invasive bladder cancer, stage I head and neck cancer, or stage I colorectal cancer

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a phase II single arm trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hormone Therapy and Radiation<br>Patients enrolled in this study will receive ADT for 6 months which will consist of bicalutamide 50 mg PO daily starting approximately 1-2 weeks before leuprolide 22.5mg injected every 3 months. The HDR prostate brachytherapy procedure will be performed approximately 3 months after starting ADT to allow for potential radiosensitization and cytoreduction. Approximately 4 weeks after the HDR boost, patients will receive image-guided, intensity-modulated, hypofractionated radiation therapy targeting the prostate, seminal vesicles and pelvic lymph nodes to a dose of 25 Gy in 5 fractions delivered daily. | Biological: Androgen deprivation therapy (ADT)<br>* ADT will include bicalutamide 50 mg PO daily started 1-2 weeks before leuprolide 22.5mg IM or SQ delivered every 3 months x 2. Bicalutamide will be continued through radiation and then discontinued on the day of the last fraction. Leuprolide can be given at different doses, but must be given for a total planned duration of 6 months.<br>Radiation: Brachytherapy<br>* After approximately 3 months (+/- 1 month) of neoadjuvant ADT, patients will undergo general anesthesia for outpatient transperineal high dose rate (HDR) interstitial prostate brachytherapy implant.<br>Radiation: Hypofractionated pelvic External beam radiation<br>* Patients will receive image-guided, intensity-modulated, hypofractionated radiation therapy targeting the prostate, seminal vesicles and pelvic lymph nodes to a dose of 25 Gy in 5 fractions delivered daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant metastatic disease-free (DMF) rate | Time to distant metastases will be estimated from the date of enrollment until distant metastases | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate |  | Between 24-36 months after radiation | 
| Cumulative incidence of biochemical failure |  | 3 years | 
| Overall survival rate |  | 3 years | 
| Acute and late physician-scored toxicity | Using CTCAE v5.0. NCI Common Toxicity Criteria. The NCI scales are simple to complete and provide a means for assessing patient symptoms. Only the CTCAE v 5.0 will be used in toxicity grading. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated Pelvic Radiation, Brachytherapy Boost, NCCN High-Risk Prostate Cancer, Low-Intermediate Risk Decipher Genomic Score, Androgen Deprivation, 21-405