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Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Cancer, Prostate Neoplasms

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Trial Information

Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer

Androgen deprivation has been the principal means of controlling advanced prostate cancer,
but does not cure the disease and all patients ultimately progress if the tumor is not
eliminated with definitive local therapy. It has been demonstrated that despite androgen
deprivation with LHRH agonists or orchiectomy, prostate tissue and prostate cancer maintain
levels of androgens which are more than adequate to stimulate the androgen receptor. These
levels of androgen may continue to stimulate the receptor and allow both survival of tumor
cells and induction of resistance by overexpression of the receptor. The presumption that
standard androgen deprivation achieves the optimal level of androgen suppression for
patients is based on the levels of androgen achieved with castration, which achieves
relatively short term control of cancer in the majority of patients. The hypothesis of this
study is that more effective suppression of the androgen axis through elimination of adrenal
androgens and more effective suppression of conversion to dihydrotestosterone will lower
intraprostatic androgen levels, minimizing activation of the androgen receptor and
augmenting apoptosis. We propose to test this hypothesis in a prospective, randomized
trial, administering neoadjuvant androgen deprivation therapy of different types prior to
radical prostatectomy for patients with clinically localized prostate cancer for 3 months.

Plan of therapy

Patients with clinically localized (cT1-T2) prostate cancer, at intermediate-high risk for
relapse who are candidates for radical prostatectomy will be treated with one of three

- Goserelin with dutasteride

- Goserelin with bicalutamide and dutasteride

- Goserelin with bicalutamide and dutasteride and ketoconazole

Patients will undergo radical prostatectomy 3 months after initiation of treatment.

Preoperative and intraoperative biopsies of the prostate gland will be utilized for analysis
of prostatic hormones, gene expression and apoptosis.

Inclusion Criteria:

1. Men 18 years or older with a histologic diagnosis of clinically localized prostate
cancer prior to radical prostatectomy as defined by:

- Clinical stage T1-T2b

- PSA less than 20

- Gleason score 7-10

2. Patient's tumor must be considered surgically resectable .

3. ECOG performance status of 0-1.

4. Life expectancy greater than 2 years.

5. Able to understand and give informed consent.

6. Laboratory values must be within specified limits.

Exclusion Criteria:

1. Patients with locally advanced or high risk disease not meeting the criteria defined

2. Patients who have a total testosterone less than 280 ng/dL.

3. Patients who are receiving any other investigational therapy.

4. Patients with an active serious infection or other serious underlying medical

5. Dementia or significantly altered mental status that would prohibit the understanding
and/or giving of informed consent.

6. Histologic evidence of small cell carcinoma of the prostate.

7. Patients who are currently receiving active therapy for other neoplastic disorders.

8. Patients who are receiving any androgens, estrogens or progestational agents.

9. Patients who are taking drugs or herbal supplements which affect androgen metabolism
(e.g., spironolactone, aprepitant, bexarotene, clarithromycin, itraconazole,
ketoconazole, St. John's wort).

10. Patients who have chronic active hepatitis.

11. Patients taking any of the following medications who cannot discontinue these
medications for three months during administration of ketoconazole; statin
cholesterol medications, cyclosporine, isoniazid, rifampin, terfenadine, triazolam or

12. Patients who have history of cerebrovascular accident, deep venous thrombosis,
pulmonary emboli, unstable angina or clinical congestive heart failure.

13. Medical conditions, which, in the opinion of the investigators would jeopardize
either the patient or the integrity of the data obtained.

14. Patients unwilling to use contraceptives while on study.

15. Patients with a risk of nodal involvement of greater than 10% as defined by the
Partin tables should have received a bone scan and CT of the pelvis prior to
screening for the study as part of standard of care.

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary endpoint of the study is to evaluate the effect of different combinations of anti-androgen medicines on androgen levels in the prostate tissue

Outcome Time Frame:

pre- and post-treatment

Safety Issue:


Principal Investigator

R. Bruce Montgomery, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Washington; Seattle Cancer Care Alliance; VA Puget Sound HCS


United States: Institutional Review Board

Study ID:

01253 - Committee 1



Start Date:

July 2006

Completion Date:

February 2012

Related Keywords:

  • Cancer
  • Prostate Neoplasms
  • Neoplasms
  • Prostatic Neoplasms



University of Washington Seattle, Washington  98195
Veterans' Administration Puget Sound Health Care System (VAPSHCS) Seattle, Washington  98108-1532