Ignite Creation Date:
2024-05-05 @ 4:47 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00311623
Status:
COMPLETED
Last Update Posted:
2019-02-22
First Post:
2006-04-05
Brief Title:
Sirolimus Before Surgery in Treating Patients With Advanced Localized Prostate Cancer
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
A Pharmacodynamic Study of Pre-Prostatectomy Rapamycin in Men With Advanced Localized Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2019-02
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:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy such as sirolimus work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing
PURPOSE This clinical trial is studying the best dose of sirolimus and to see how well it works before surgery in treating patients with advanced localized prostate cancer
PURPOSE This clinical trial is studying the best dose of sirolimus and to see how well it works before surgery in treating patients with advanced localized prostate cancer
Detailed Description:
OBJECTIVES
Primary
Determine the pharmacodynamically optimal dose POD of continuous daily oral sirolimus rapamycin in patients with advanced localized prostate cancer when given prior to radical prostatectomy as measured by tumor S6 kinase inhibition by immunohistochemistry IHC
Determine the proportion of men with downstream target inhibition in prostate tumor tissue at the POD using paired tumor biopsies from before and after rapamycin administration
Correlate tumor pharmacodynamic PD efficacy with a surrogate marker of tumor PD efficacy peripheral blood mononuclear cell PBMC S6 kinase activity inhibition
Secondary
Characterize the serum and prostate tissue pharmacokinetics of daily oral rapamycin at 2 dose levels
Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment Akt activity and PTEN loss by IHC in prostate cancer
Describe the relationship between PD inhibition with the mTOR inhibitor rapamycin and pretreatment prostate biopsy Gleason sum Ki-67 index of proliferation Akt activity p27 IHC and PTEN
Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis activated caspase 3 and reduction in markers of proliferation change in Ki-67 in prostate tumor specimens
Quantify and characterize the toxicity of daily continuous rapamycin at 2 dose levels in generally healthy men with prostate cancer prior to surgery
Evaluate the activity of rapamycin in prostate cancer as measured in prostate specific antigen response prior to surgery
OUTLINE This is a multicenter dose-escalation study
Patients receive oral sirolimus rapamycin once daily on days 1-14 in the absence of unacceptable toxicity
Cohorts of 12-21 patients receive escalating doses of rapamycin until the pharmacodynamically optimal dose is determined
Patients undergo radical prostatectomy on day 15
Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and correlative biomarker studies
After completion of study treatment patients are followed at 30 and 90 days
PROJECTED ACCRUAL A total of 42 patients will be accrued for this study
Primary
Determine the pharmacodynamically optimal dose POD of continuous daily oral sirolimus rapamycin in patients with advanced localized prostate cancer when given prior to radical prostatectomy as measured by tumor S6 kinase inhibition by immunohistochemistry IHC
Determine the proportion of men with downstream target inhibition in prostate tumor tissue at the POD using paired tumor biopsies from before and after rapamycin administration
Correlate tumor pharmacodynamic PD efficacy with a surrogate marker of tumor PD efficacy peripheral blood mononuclear cell PBMC S6 kinase activity inhibition
Secondary
Characterize the serum and prostate tissue pharmacokinetics of daily oral rapamycin at 2 dose levels
Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment Akt activity and PTEN loss by IHC in prostate cancer
Describe the relationship between PD inhibition with the mTOR inhibitor rapamycin and pretreatment prostate biopsy Gleason sum Ki-67 index of proliferation Akt activity p27 IHC and PTEN
Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis activated caspase 3 and reduction in markers of proliferation change in Ki-67 in prostate tumor specimens
Quantify and characterize the toxicity of daily continuous rapamycin at 2 dose levels in generally healthy men with prostate cancer prior to surgery
Evaluate the activity of rapamycin in prostate cancer as measured in prostate specific antigen response prior to surgery
OUTLINE This is a multicenter dose-escalation study
Patients receive oral sirolimus rapamycin once daily on days 1-14 in the absence of unacceptable toxicity
Cohorts of 12-21 patients receive escalating doses of rapamycin until the pharmacodynamically optimal dose is determined
Patients undergo radical prostatectomy on day 15
Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and correlative biomarker studies
After completion of study treatment patients are followed at 30 and 90 days
PROJECTED ACCRUAL A total of 42 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NA_00001011 | OTHER | JHM IRB | httpsreporternihgovquickSearchP30CA006973 |
| P30CA006973 | NIH | None | None |
| CDR0000468942 | OTHER | None | None |