Efficacy and Toxicity of Bicalutamide and Dutasteride vs. Standard Care for Prostate Cytoreduction for Brachytherapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if a combination of neoadjuvant dutasteride and bicalutamide has the same efficacy and less toxicity than standard treatment with an LHRH agonist and bicalutamide for prostate cytoreduction prior to permanent implant brachytherapy.

Detailed Description
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Permanent implant prostate brachytherapy is recognized as the treatment method for prostate cancer that results in the least amount of sexual side effects including erectile dysfunction (ED). However prostate brachytherapy is often limited to patients with a prostate volume less than 50cc because of dosimetric and technical considerations. To counter this fact patients with a prostate larger than 50cc are offered neoadjuvant hormonal therapy to reduce their prostate volume to a value less than 50cc. The pharmacological method most often employed involves treatment with an LHRH agonist, which also involves multiple adverse effects for patients including ED in the majority of patients. This approach may also involve other disadvantages including a possibility of increased cardiovascular mortality a possible increase in urinary toxicity and a reduction in health-related quality of life in patients treated with neoadjuvant hormonal therapy. Despite theses facts, neoadjuvant hormonal therapy remains essentially the sole method used to reduce prostate volume prior to prostate brachytherapy. One study has evaluated the efficacy of a neoadjuvant regimen without an LHRH agonist, comprised of Dutasteride and Bicalutamide to reduce prostate volume. This treatment could theoretically have fewer effects on sexual function and quality of life and could also possibly reduce urinary toxicity of brachytherapy. Nonetheless, these factors have never been evaluated. The cytoreductive efficacy of Bicalutamide and Dutasteride have never been directly compared to standard treatments. The current study is necessary to determine the effects of a neoadjuvant regimen of Bicalutamide and Dutasteride on prostate volume, sexual function, urinary toxicity and quality of life as compared to standard treatment. If it can be determined that there is an advantage with Bicalutamide and Dutasteride this regimen could become a standard of care for prostate cytoreduction prior to brachytherapy.

Official Title
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Phase II Study of Bicalutamide and Dutasteride for Prostate Cytoreduction Prior to Permanent Implant I-125 Prostate Brachytherapy

Conditions
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Prostate Cancer, Erectile Dysfunction, Lower Urinary Tract Symptoms

Intervention / Treatment
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* Drug: administration of a LHRH agonist and Bicalutamide
* Drug: administration of Bicalutamide, Dutasteride and Tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male sex Diagnosis of prostate adenocarcinoma as confirmed by prostate biopsy Prostate cancer with stage T1a, T1b T2a or T2b Nx Mx as determined by clinical examination Gleason score of 6 or less or 7 (3+4)* * If Gleason score is 7(3+4) patient must have less than 30% of biopsied tissue positive Serum PSA of ≤ 15ng/ml during the month before study entry Prostate volume ≥ 45cc Normal serum testosterone during the month before study entry Availability for treatment and follow-up visits Having signed required consent form before study entry Exclusion Criteria: Abnormal Liver Function tests (>2x normal AST or ALT and/or >1.5x normal bilirubin) Prostate volume less than 50 cc History of hormonal treatment including any of the above: LHRH agonists, antiandrogens during the year before study entry Use of a 5 alpha reductase inhibitor for more than one month during the year prior to study entry History of pelvic irradiation History of past chemotherapy History of TURP History of past treatment for prostate cancer Known hypersensitivity to Dutasteride or Bicalutamide Co-morbid disease possibly compromising treatment compliance History of DVT or pulmonary embolism Anticoagulation with coumarin Inability to give consent

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LHRH agonist<br>Administration of a 3-month treatment with an LHRH agonist (chosen by the treating radiation oncologist) and Bicalutamide 50 mg daily for the first month of treatment with the LHRH agonist. | Drug: administration of a LHRH agonist and Bicalutamide<br>* 3-month treatment with an LHRH agonist chosen by the treating radiation oncologist and Bicalutamide 50 mg daily for the first month of treatment with the LHRH agonist.<br>* Other names: Bicalutamide(Casodex);|
| Experimental: Dutasteride, Bicalutamide, Tamoxifen<br>Administration of Dutasteride given at dose of 0.5 mg daily starting three months prior to day of implant procedure and continued for 3 months up until procedure. Bicalutamide: given at a dose of 50 mg daily for 3 the same 3 month period as dutasteride Tamoxifen: given at dose of 10 mg daily for 3 months that dutasteride and bicalutamide are administered. | Drug: administration of Bicalutamide, Dutasteride and Tamoxifen<br>* Dutasteride given at dose of 0.5 mg daily starting three months prior to day of implant procedure and continued for 3 months up until procedure. Bicalutamide: given at a dose of 50 mg daily for 3 the same 3 month period as dutasteride Tamoxifen: given at dose of 10 mg daily for 3 months that dutasteride and bicalutamide are administered.<br>* Other names: Tamoxifen (Nolvadex);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total prostate volume | Trans rectal ultra sound 3 dimensional volume evaluation | 3 months after start of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPIC questionnaire urinary function and bother scores | Expanded Prostate Cancer Index Composite | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| EPIC questionnaire sexual function and bother scores | Expanded Prostate Cancer Index Composite | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| EPIC questionnaire bowel function and bother scores | Expanded Prostate Cancer Index Composite | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| EPIC questionnaire hormonal function and bother scores | Expanded Prostate Cancer Index Composite | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| IPSS scores | International Prostate Symptom Score (I-PSS) | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| Acute urinary retention rates | Common Terminology Criteria for Adverse Events (CTCAE) | 0 to 6 months post-implant | 
| SF-12 Quality of life questionnaire results | International Quality of Life Assessment - Short Form | baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| Rate of gynecomastia and breast tenderness | Common Terminology Criteria for Adverse Events (CTCAE) | 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 
| Serum testosterone | testosterone blood level | 3 months pre-implant, pre-implant, 3,6,12,18 and 24 months post-implant | 
| Anemia | haemoglobin blood level | baseline, pre-implant, 3,6,12,18 and 24 months post-implant | 
| Abnormal liver function tests | Blood level of Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), Bilirubin, Gamma-glutamyltransferase (GGT), L-lactate dehydrogenase (LD). | 6 weeks pre-implant, pre-implant, 3 months post-implant | 
| Serum PSA | serum testosterone blood level | baseline, pre-implant, 3,6,12,18 and 24 months post-implant | 
| Adverse events recording | Common Terminology Criteria for Adverse Events (CTCAE) | 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Brachytherapy, Cytoreduction, Sexual function, Toxicity