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

Phase 2
Completed
Conditions
Lower Urinary Tract Symptoms
Prostate Cancer
Erectile Dysfunction
Interventions
Drug: administration of Bicalutamide, Dutasteride and Tamoxifen
Drug: administration of a LHRH agonist and Bicalutamide
Registration Number
NCT00866554
Lead Sponsor
CHU de Quebec-Universite Laval
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dutasteride, Bicalutamide, Tamoxifenadministration of Bicalutamide, Dutasteride and TamoxifenAdministration 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.
LHRH agonistadministration of a LHRH agonist and BicalutamideAdministration 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.
Primary Outcome Measures
NameTimeMethod
Total prostate volume3 months after start of therapy

Trans rectal ultra sound 3 dimensional volume evaluation

Secondary Outcome Measures
NameTimeMethod
EPIC questionnaire sexual function and bother scoresbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Expanded Prostate Cancer Index Composite

Anemiabaseline, pre-implant, 3,6,12,18 and 24 months post-implant

haemoglobin blood level

EPIC questionnaire urinary function and bother scoresbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Expanded Prostate Cancer Index Composite

IPSS scoresbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

International Prostate Symptom Score (I-PSS)

Acute urinary retention rates0 to 6 months post-implant

Common Terminology Criteria for Adverse Events (CTCAE)

EPIC questionnaire bowel function and bother scoresbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Expanded Prostate Cancer Index Composite

EPIC questionnaire hormonal function and bother scoresbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Expanded Prostate Cancer Index Composite

Rate of gynecomastia and breast tenderness6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Common Terminology Criteria for Adverse Events (CTCAE)

Serum testosterone3 months pre-implant, pre-implant, 3,6,12,18 and 24 months post-implant

testosterone blood level

SF-12 Quality of life questionnaire resultsbaseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

International Quality of Life Assessment - Short Form

Abnormal liver function tests6 weeks pre-implant, pre-implant, 3 months post-implant

Blood level of Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), Bilirubin, Gamma-glutamyltransferase (GGT), L-lactate dehydrogenase (LD).

Serum PSAbaseline, pre-implant, 3,6,12,18 and 24 months post-implant

serum testosterone blood level

Adverse events recording6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant

Common Terminology Criteria for Adverse Events (CTCAE)

Trial Locations

Locations (1)

CHUQ- Hotel-Dieu de Quebec

🇨🇦

Quebec, Canada

CHUQ- Hotel-Dieu de Quebec
🇨🇦Quebec, Canada

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