Efficacy and Toxicity of Bicalutamide and Dutasteride vs. Standard Care for Prostate Cytoreduction for Brachytherapy - Full Text View

Sponsors and Collaborators:	Centre hospitalier universitaire de Québec GlaxoSmithKline
Information provided by:	Centre hospitalier universitaire de Québec
ClinicalTrials.gov Identifier:	NCT00866554

Purpose

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.

Condition	Intervention	Phase
Prostate Cancer Erectile Dysfunction Urinary Toxicity	Drug: LHRH agonist and Bicalutamide Drug: Bicalutamide, Dutasteride and Tamoxifen	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II Study of Bicalutamide and Dutasteride for Prostate Cytoreduction Prior to Permanent Implant I-125 Prostate Brachytherapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Erectile Dysfunction Prostate Cancer

Drug Information available for: Tamoxifen Gonadorelin Gonadorelin hydrochloride Tamoxifen citrate Bicalutamide Dutasteride LH-RH

U.S. FDA Resources

Further study details as provided by Centre hospitalier universitaire de Québec:

Primary Outcome Measures:

Total prostate volume [ Time Frame: 3 months after start of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

EPIC questionnaire urinary function and bother scores [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
EPIC questionnaire sexual function and bother scores [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
EPIC questionnaire bowel function and bother scores [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
EPIC questionnaire hormonal function and bother scores [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
IPSS scores [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
Acute urinary retention rates [ Time Frame: 0 to 6 months post-implant ] [ Designated as safety issue: No ]
SF-12 Quality of life questionnaire results [ Time Frame: baseline, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
Rate of gynecomastia and breast tenderness [ Time Frame: 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: Yes ]
Serum testosterone [ Time Frame: 3 months pre-implant, pre-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
Anemia [ Time Frame: baseline, pre-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
Abnormal liver function tests [ Time Frame: 6 weeks pre-implant, pre-implant, 3 months post-implant ] [ Designated as safety issue: Yes ]
Serum PSA [ Time Frame: baseline, pre-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: No ]
Adverse events recording [ Time Frame: 6 weeks pre-implant, pre-implant, 6 weeks post-implant, 3,6,12,18 and 24 months post-implant ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	88
Study Start Date:	March 2009
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 3-month treatment with an LHRH agonist chosen by the treating radiation oncologist Bicalutamide 50 mg daily for the first month of treatment with the LHRH agonist.	Drug: 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.
2: Experimental 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: 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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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 ≥ 50cc
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866554

Contacts

Contact: Andre-Guy Martin, MD, Msc	418-691-5264	andre-guy.martin@mail.chuq.qc.ca
Contact: Josée Allard, RN	418-525-4444 ext 16730	Josee.Allard@chuq.qc.ca

Locations

Canada
CHUQ- Hotel-Dieu de Quebec	Recruiting
Quebec, Canada, G1R 2J6
Contact: Andre-Guy Martin, MD MSc 418-691-5263 andre-guy.martin@mail.chuq.qc.ca
Contact: Josee Allard, RN 418-525-4444 ext 16730 Josee.Allard@chuq.qc.ca

Sponsors and Collaborators

Centre hospitalier universitaire de Québec

GlaxoSmithKline

Investigators

Principal Investigator:

Andre-Guy Martin, MD

CHUQ-Hotel-Dieu de Québec

More Information

No publications provided

Responsible Party:	CHUQ Hotel-Dieu de Quebec, Département de radio-oncologie ( Andre-Guy Martin )
Study ID Numbers:	DUT112661, Health Canada-112661
Study First Received:	March 19, 2009
Last Updated:	April 17, 2009
ClinicalTrials.gov Identifier:	NCT00866554 History of Changes
Health Authority:	Canada: Health Canada

Keywords provided by Centre hospitalier universitaire de Québec:

Prostate
Brachytherapy
Cytoreduction
Sexual function
Toxicity

Study placed in the following topic categories:

Sexual Dysfunctions, Psychological
Estrogen Antagonists
Estrogens
Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents, Hormonal
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Urogenital Neoplasms
Selective Estrogen Receptor Modulators
Genital Diseases, Male

Hormones
Tamoxifen
Dutasteride
Estrogen Receptor Modulators
Androgen Antagonists
Sexual Dysfunction, Physiological
Mental Disorders
Bicalutamide
Prostatic Neoplasms
Erectile Dysfunction
Androgens

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Prostatic Diseases
Genital Neoplasms, Male
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Sexual Dysfunction, Physiological
Neoplasms by Site
Mental Disorders
Therapeutic Uses

Sexual Dysfunctions, Psychological
Estrogen Antagonists
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Genital Diseases, Male
Tamoxifen
Sexual and Gender Disorders
Pharmacologic Actions
Dutasteride
Androgen Antagonists
Neoplasms
Bicalutamide
Erectile Dysfunction
Prostatic Neoplasms

ClinicalTrials.gov processed this record on August 25, 2009