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

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

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.

Study Overview

• Status: Completed
• Conditions: Lower Urinary Tract Symptoms; Erectile Dysfunction; Prostate Cancer
• Intervention / Treatment: Drug: administration of a LHRH agonist and Bicalutamide; Drug: administration of Bicalutamide, Dutasteride and Tamoxifen

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • CHUQ- Hotel-Dieu de Quebec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LHRH agonist; 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; 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.; Other Names: Bicalutamide(Casodex)
Experimental: Dutasteride, Bicalutamide, Tamoxifen; 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; 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.; Other Names: Bicalutamide (Casodex); Dutasteride (Avodart); Tamoxifen (Nolvadex)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Andre-Guy Martin, MD, CHUQ-Hotel-Dieu de Québec

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimated): March 20, 2009

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Brachytherapy; Toxicity; Prostate; Sexual function; Cytoreduction
• Additional Relevant MeSH Terms: Mental Disorders; Urological Manifestations; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Lower Urinary Tract Symptoms; Erectile Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Androgen Antagonists; 5-alpha Reductase Inhibitors; Tamoxifen; Bicalutamide; Dutasteride
• Other Study ID Numbers: DUT112661; Health Canada-112661 (Other Grant/Funding Number: GSK)