Clinical trial NCT00866554: Efficacy and Toxicity of Bicalutamide and Dutasteride vs. Standard Care for Prostate Cytoreduction for Brachytherapy
Official title: Phase II Study of Bicalutamide and Dutasteride for Prostate Cytoreduction Prior to Permanent Implant I-125 Prostate Brachytherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Erectile Dysfunction
Lower Urinary Tract Symptoms
Keywords: Prostate
Brachytherapy
Cytoreduction
Sexual function
Toxicity
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2009-03-20
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total prostate volume
timeFrame: 3 months after start of therapy
Secondary outcomes:
measure: EPIC questionnaire urinary function and bother scores
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: EPIC questionnaire sexual function and bother scores
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: EPIC questionnaire bowel function and bother scores
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: EPIC questionnaire hormonal function and bother scores
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: IPSS scores
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: Acute urinary retention rates
timeFrame: 0 to 6 months post-implant
measure: SF-12 Quality of life questionnaire results
timeFrame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: Rate of gynecomastia and breast tenderness
timeFrame: 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
measure: Serum testosterone
timeFrame: 3 months pre-implant, pre-implant, 3,6,12,18 and 24 months post-implant
measure: Anemia
timeFrame: baseline, pre-implant, 3,6,12,18 and 24 months post-implant
measure: Abnormal liver function tests
timeFrame: 6 weeks pre-implant, pre-implant, 3 months post-implant
measure: Serum PSA
timeFrame: baseline, pre-implant, 3,6,12,18 and 24 months post-implant
measure: Adverse events recording
timeFrame: 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: CHUQ- Hotel-Dieu de Quebec
Study officials:
affiliation: CHUQ-Hotel-Dieu de Québec
name: Andre-Guy Martin, MD
role: PRINCIPAL_INVESTIGATOR
References: