Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00167648
Status:
COMPLETED
Last Update Posted:
2009-01-19
First Post:
2005-09-09
Brief Title:
Neoadjuvant Estradiol or Androgen Deprivation in Clinically Localized Prostate Cancer
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
Neoadjuvant Estradiol or Androgen Deprivation in Clinically Localized Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2009-01
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:
NE2
Brief Summary:
Prostate cancer is the most commonly diagnosed cancer among males in the US More than 220000 men will be diagnosed with prostate cancer in the USA this year and more that 31000 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
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
Detailed Description:
Estrogens are effective means of treating advanced prostate cancer In randomized studies estrogens have better cancer control rates than orchiectomy alone suggesting that estrogen efficacy is not limited to its ability to suppress testosterone One hypothesis is that estrogens modulate immunity to prostate cancer through direct activation of effector cells and by upregulating cytokines in prostatic stroma Administration of estrogen in murine models induces infiltration of normal prostate with T lymphocytes even in castrate male animals potentially through induction of autoimmunity to normally cryptic prostate antigens Estrogens activate multiple immune effectors and autoimmunity in a broad variety of experimental settings suggesting upregulation of immune recognition on many levels Pilot data demonstrates that estrogens upregulate expression of interferon regulated genes major histocompatibility antigens MHC on prostate cancer and increase both number and activation of natural killer NK cells Other groups have shown that standard forms of androgen deprivation also induce immunity against both normal and malignant prostate tissue We propose to test the hypothesis that administration of estrogen andor androgen deprivation induces immune recognition of prostate cancer in humans through upregulation of major histocompatibility antigens on tumor and induction of tumor specific immunity The specificity of estrogen effect will be tested by comparing measures of immunity in patients treated with estradiol androgen deprivation or no neoadjuvant therapy
Plan of therapy
The specific aims of this proposal are
1 To treat patients with clinically localized low to intermediate risk prostate cancer who are candidates for radical prostatectomy with either standard androgen deprivation prior to surgery neoadjuvant androgen deprivation or neoadjuvant transdermal estradiol Patients will undergo radical prostatectomy 21 days after initiation of treatment
2 To evaluate radical prostatectomy specimens obtained from these patients for expression of MHC class I and II and NK ligands MICA and MICB in prostate carcinoma and adjacent prostate by immunohistochemistry IHC and Western analysis
3 To evaluate tumor tissue for infiltration by clonal T lymphocytes NK cells and plasmacytoid dendritic cells using IHC and spectratyping of T cell receptor gene rearrangements
4 To evaluate patients for the induction of tumor specific antibodies using patient immunoglobulin collected before and after neoadjuvant therapy SEREX
5 To evaluate patients for induction of NK cells and upregulation of the NK receptor NKG2D on patient lymphocytes by androgen deprivation and estradiol
6 To evaluate the effects of androgen deprivation and estradiol on induction of plasma and tissue levels of interferon gamma alpha beta IL-4 and GM-CSF by ELISA and ribonuclease protection assay
Plan of therapy
The specific aims of this proposal are
1 To treat patients with clinically localized low to intermediate risk prostate cancer who are candidates for radical prostatectomy with either standard androgen deprivation prior to surgery neoadjuvant androgen deprivation or neoadjuvant transdermal estradiol Patients will undergo radical prostatectomy 21 days after initiation of treatment
2 To evaluate radical prostatectomy specimens obtained from these patients for expression of MHC class I and II and NK ligands MICA and MICB in prostate carcinoma and adjacent prostate by immunohistochemistry IHC and Western analysis
3 To evaluate tumor tissue for infiltration by clonal T lymphocytes NK cells and plasmacytoid dendritic cells using IHC and spectratyping of T cell receptor gene rearrangements
4 To evaluate patients for the induction of tumor specific antibodies using patient immunoglobulin collected before and after neoadjuvant therapy SEREX
5 To evaluate patients for induction of NK cells and upregulation of the NK receptor NKG2D on patient lymphocytes by androgen deprivation and estradiol
6 To evaluate the effects of androgen deprivation and estradiol on induction of plasma and tissue levels of interferon gamma alpha beta IL-4 and GM-CSF by ELISA and ribonuclease protection assay
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