Neoadjuvant Estradiol or Androgen Deprivation in Clinically Localized Prostate Cancer

NCT00167648 | Completed Phase 2 DMC

• 1 other identifier: 05-5564-V 01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

Prostate cancer is the most commonly diagnosed cancer among males in the U.S. More than 220,000 men will be diagnosed with prostate cancer in the USA this year and more that 31,000 will die of this disease. Androgen deprivation, the elimination of testosterone and its active metabolites, remains the single most effective intervention available for the treatment of advanced prostate carcinoma. Androgen deprivation induces an immune response to normal prostate and prostate cancer, which is usually short-lived. Estradiol induces activation of many arms of the immune system and may be a more effective and long lasting means of inducing immunity to prostate tissue. This study will treat clinically localized prostate cancer patients with either estrogens, or standard androgen deprivation without estrogens, prior to prostatectomy in order more completely to describe immune regulation by estradiol in men. Control tissue from patients who have not been treated with androgen deprivation will be procured from the Northwest Special Projects in Oncology Research Excellence (SPORE) tissue core and used as comparisons against the cancers treated before prostatectomy. Tumors removed at prostatectomy, tissue samples and blood samples will be assessed for immune system changes.

Conditions

Cancer; Prostate Neoplasms

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the study is to evaluate the induction of tumor and prostate-specific immunity by androgen deprivation and estradiol administration.

  End of Study

Secondary Outcomes (1)

• Effects of androgen deprivation and estradiol administration on tumor infiltration by T lymphocytes, NK cells, and plasmacytoid dendritic cells

  End of Study

Study Arms (2)

A

ACTIVE COMPARATOR

Leuprolide 7.5 mg or Goserelin 3.6 mg

Drug: Leuprolide or goserelin

B

EXPERIMENTAL

Transdermal estradiol 0.6 mg q 3 days

Drug: Transdermal estradiol

Interventions

Leuprolide or goserelin DRUG

Leuprolide 7.5 mg (4-week depot) or goserelin 3.6 mg (4-week depot)

A

Transdermal estradiol DRUG

Estradiol patches, six at 0.1 mg each, changed every 3-4 days

B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men 18 years or older with a histologic diagnosis of low to intermediate risk prostate cancer prior to radical prostatectomy as defined by:
• Clinical stage T1-T2b
• PSA \< 20
• Gleason score \< 7
• Patients who have more than one of the following prognostic factors: T2b, Gleason 7, PSA 10-20 are not eligible.
• Patient's tumor must be considered surgically resectable as determined by a urologic evaluation
• ECOG performance status of 0-1
• Life expectancy greater than 2 years
• Able to understand and give informed consent
• Patients must agree not to take dietary phytoestrogens or other estrogen containing supplements

You may not qualify if:

• Patients with locally advanced or high-risk disease as defined above.
• Patients who have a testosterone less than 280 ng/dL.
• Patients who have evidence of cerebrovascular accident or ischemia, recent deep venous thrombosis, pulmonary emboli, unstable angina or clinical congestive heart failure.
• Patients who are receiving any other investigational therapy.
• Patients with an active serious infection or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment.
• Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent.
• Patients with immunodeficiency or on oral corticosteroids
• Histologic evidence of small cell carcinoma of the prostate.
• Patients with a prior history of myocardial infarction, pulmonary embolism, CVA or atrial fibrillation.
• Patients with active thrombophlebitis.
• Patients with evidence of active angina as evidenced by chest pain responsive to sublingual nitroglycerin or other anginal equivalent.
• Medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained
• Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible for study.
• Patients taking any of the following medications who cannot discontinue these medications for three weeks during administration of androgen deprivation: aprepitant, bexarotene, clarithromycin, itraconazole, ketoconazole, St. John's wort.

Sponsors & Collaborators

• University of Washington: lead
• Pacific Northwest SPORE: collaborator

Study Sites (2)

VA Puget Sound Health Care System

Seattle, Washington, 98119, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195-6158, United States

Location

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms

Interventions

Leuprolide; Goserelin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• R. Bruce Montgomery, MD

  University of Washington; VA Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: March 1, 2005
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: January 19, 2009

Record last verified: 2009-01

Locations

US (2)