Fairly Brief Androgen Suppression and Stereotactic Radiotherapy for High Risk Prostate Cancer - Protocol 2

Study Overview
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Brief Summary
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This study will explore the combination of a stereotactic body radiation therapy (SBRT) approach combined with one year of luteinizing hormone releasing hormone (LHRH) agonist for older men with high risk prostate cancer, or men unwilling to undertake conventionally fractionated therapy and three years of adjuvant hormone therapy. The purpose of this study is to examine the safety of a shorter course of radiation treatment combined wtih androgen deprivation therapy.

Detailed Description
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Randomized controlled trials have established the improved efficacy (better biochemical control and disease free survival) of combined radical radiation (70-80 Gy over 7-8 weeks) combined with long term hormone therapy (2-3 years of adjuvant LHRH agonist) compared to a primary hormone therapy or radiation therapy alone in men with locally advanced/high risk disease. While this approach may be tolerable in fit individuals, this combination may not be well tolerated by frail individuals, or those who live at a distance who may find it difficult to attend for 7 weeks of radiation treatments. Those individuals with co-morbidities such as diabetes, coronary artery disease or osteoporosis may have those conditions exacerbated by long term hormone therapy. The combination of short course radiation and hormone therapy was explored in the FASTR trial. As part of the trial, patients received 12 months of hormone therapy with radiation treatment to the pelvic lymph nodes (dose of 25 Gy in 5 fractions, 1 fraction per week) concomitant with radiation treatment to the prostate (dose of 40 Gy in 5 fractions, 1 fraction per week). The study was discontinued due to toxicity. For the FASTR-2 study, these concerns are being addressed through the use of a lower total dose to the prostate (35 Gy in 5 fractions, 1 fraction per week). Given the uncertainty of the benefit of pelvic nodal radiation in prostate cancer, it was decided to omit the pelvic nodal radiation in the FASTR-2 study. In addition, given the recent evidence supporting the equivalence of 18 months of hormone therapy, compared to 36 months, it was decided to lengthen the duration of hormone therapy in the FASTR-2 study to 18 months (versus 12 months in the FASTR study).

Official Title
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Fairly Brief Androgen Suppression and Stereotactic Radiotherapy for High Risk Prostate Cancer - Protocol 2

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Radiation
* Drug: Androgen Suppression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk prostate cancer Has had multidisciplinary consultation with radiation oncologist and urologist Age >70 or refuses standard treatment No evidence of extra-prostatic disease on screening bone scan and CT scan (non-contrast CT used for CT simulation acceptable) Signed written and voluntary informed consent provided. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Patients not meeting the eligibility criteria Prior pelvic radiotherapy or brachytherapy Use of anti-coagulation (low molecular weight heparin or Coumadin) History of inflammatory bowel disease, Crohn's disease, diverticulitis or collagen vascular disease (other than rheumatoid arthritis) Previous treatment for malignancy (other than basal or squamous cell skin cancer) within 3 years of prostate cancer diagnosis patients on androgen deprivation therapy > 2 months prior to study enrolment

Ages Eligible for Study
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Minimum Age: 70 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 |
| --- | --- |
| Experimental: Radiation plus Androgen Supression<br>Radiation plus Androgen Suppression give as stereotactic radiation 7gray (Gy) per week x 5 weeks and leuprolide 45mg every 6 months for 18 months | Radiation: Radiation<br>* Radiation: Radiotherapy 7 gray (Gy) per week over 5 weeks (35Gy)<br>Drug: Androgen Suppression<br>* Leuprolide 45mg every 6 months for a total of 18 months<br>* Other names: LHRH agonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genitourinary and Gastrointestinal Toxicity at 1 year | Genitourinary and gastrointestinal toxicity measured at year 1 of follow-up using the Common Toxicity Criteria | Year 1 of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival at 3 years | Defined by absence of clinical relapse and prostatic specific antigen (PSA) failure as per the American Society of Therapeutic Radiation and Oncology (ASTRO) Phoenix definition | 1, 2, and 3 years of follow-up | 
| Quality of Life | Measured using the Prostate Cancer Radiotherapy questionnaire | 1, 2, and 3 years of follow-up | 
| Genitourinary and Gastrointestinal Toxicity at 2 years | Genitourinary and gastrointestinal toxicity measured at year 2 of follow-up using the Common Toxicity Criteria Safety Issue? (FDAAA) Yes | Year 2 of follow-up | 
| Genitourinary and gastrointestinal toxicity measured at 3 years | Genitourinary and gastrointestinal toxicity measured at year 3 of follow-up using the Common Toxicity Criteria | Year 3 of follow-up |