Ignite Creation Date:
2024-05-05 @ 4:41 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00298155
Status:
COMPLETED
Last Update Posted:
2018-08-09
First Post:
2006-02-27
Brief Title:
Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2018-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TAPS
Brief Summary:
Prostate cancer CaP is the most commonly diagnosed cancer among males in the US and the second leading cause of cancer-related mortality More than 230000 men will be diagnosed with prostate cancer in the USA this year and more than 30000 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 This is usually achieved by surgical removal of the testes orchiectomy by suppressing production of testosterone LHRH agonists andor by blocking the androgens at receptor sites antiandrogens Unfortunately androgen suppression does not cure the disease Most patients progress within 0-5 years and all patients ultimately progress if the cancer is not eliminated during initial therapy usually prostatectomy or radiation
Hormone suppression treatment eliminates the detectable levels of testosterone in the blood However the testosterone levels in tissue remain high enough to stimulate androgen receptors Overexpression of androgen receptors is present in all cell lines which demonstrate androgen independence ie are resistant to androgen-suppressive therapy
Approximately 95 of testosterone is supplied by the testes with the remaining 5 supplied by the adrenal glands The presumption that standard androgen deprivation achieves the optimal level of androgen suppression for patients is based on the levels of androgen which result from orchiectomy However because adrenal androgen levels are unaffected by standard modes of androgen deprivation 5 of the bodys testosterone remains despite hormone therapy
The hypothesis of this study is that more effective suppression of the androgen axis through elimination of adrenal androgens and more effective suppression of testosterone metabolites will lower intraprostatic androgen levels minimizing activation of the androgen receptor and augmenting natural cell death apoptosis The investigators propose to test this hypothesis by administering neoadjuvant pre-surgery androgen deprivation therapy of different types before prostatectomy for patients with clinically localized prostate cancer The investigators will assay serum and intraprostatic androgen levels while assessing relative levels of apoptosis of normal and malignant tissue
Androgen deprivation the elimination of testosterone and its active metabolites remains the single most effective intervention available for the treatment of advanced prostate carcinoma This is usually achieved by surgical removal of the testes orchiectomy by suppressing production of testosterone LHRH agonists andor by blocking the androgens at receptor sites antiandrogens Unfortunately androgen suppression does not cure the disease Most patients progress within 0-5 years and all patients ultimately progress if the cancer is not eliminated during initial therapy usually prostatectomy or radiation
Hormone suppression treatment eliminates the detectable levels of testosterone in the blood However the testosterone levels in tissue remain high enough to stimulate androgen receptors Overexpression of androgen receptors is present in all cell lines which demonstrate androgen independence ie are resistant to androgen-suppressive therapy
Approximately 95 of testosterone is supplied by the testes with the remaining 5 supplied by the adrenal glands The presumption that standard androgen deprivation achieves the optimal level of androgen suppression for patients is based on the levels of androgen which result from orchiectomy However because adrenal androgen levels are unaffected by standard modes of androgen deprivation 5 of the bodys testosterone remains despite hormone therapy
The hypothesis of this study is that more effective suppression of the androgen axis through elimination of adrenal androgens and more effective suppression of testosterone metabolites will lower intraprostatic androgen levels minimizing activation of the androgen receptor and augmenting natural cell death apoptosis The investigators propose to test this hypothesis by administering neoadjuvant pre-surgery androgen deprivation therapy of different types before prostatectomy for patients with clinically localized prostate cancer The investigators will assay serum and intraprostatic androgen levels while assessing relative levels of apoptosis of normal and malignant tissue
Detailed Description:
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 regimens
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
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 regimens
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FHCRC-05026 | OTHER | None | None |
| 05-8538-V 01 | OTHER | None | None |
| 28741-A | OTHER | None | None |
| 01253 | OTHER | VA Puget Sound Health Care System IRB current | None |