Ignite Creation Date:
2024-05-05 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00368914
Status:
COMPLETED
Last Update Posted:
2010-08-09
First Post:
2006-08-24
Brief Title:
Sirolimus in Treating Patients With Metastatic or Unresectable Solid Tumors
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
Pharmacodynamic-Guided Dose Finding Study of Rapamycin Rapamune Sirolimus in Adult Patients With Solid Tumors
Status:
COMPLETED
Status Verified Date:
2010-08
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 Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
PURPOSE This phase I trial is studying the side effects and best dose of sirolimus in treating patients with metastatic or unresectable solid tumors
PURPOSE This phase I trial is studying the side effects and best dose of sirolimus in treating patients with metastatic or unresectable solid tumors
Detailed Description:
OBJECTIVES
Primary
Determine the pharmacodynamic optimal dose of sirolimus by evaluating p70s6 kinase inhibition in peripheral blood mononuclear cells PBMC and normal skin in patients with metastatic or unresectable solid tumors
Correlate target inhibition in tumor tissue with PBMC and normal skin target inhibition in patients whose tumors are amenable to sequential tumor biopsies
Secondary
Characterize the pharmacokinetics of sirolimus in these patients
Determine the pharmacodynamic effects of sirolimus on tumor normal skin and normal oral mucosa of these patients
Correlate the pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects
Correlate the Akt signaling pathway with pharmacodynamic endpoints
Explore pharmacokinetic-pharmacodynamic and toxicodynamic relationships of sirolimus in these patients
Quantify the toxicity of sirolimus in these patients
Evaluate preliminarily the activity of sirolimus in these patients
OUTLINE This is a prospective dose-escalation study
Patients receive oral sirolimus once daily on days 1-28 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity The pharmacodynamic optimal dose is considered the dose at which 10 patients are treated without requiring further dose escalation
Patients undergo blood collection tumor tissue and normal skin biopsies and oral mucosal smears periodically for pharmacodynamic pharmacokinetic and biomarker correlative studies
After completion of study treatment patients are followed at 4 weeks
PROJECTED ACCRUAL A total of 30 patients will be accrued for this study
Primary
Determine the pharmacodynamic optimal dose of sirolimus by evaluating p70s6 kinase inhibition in peripheral blood mononuclear cells PBMC and normal skin in patients with metastatic or unresectable solid tumors
Correlate target inhibition in tumor tissue with PBMC and normal skin target inhibition in patients whose tumors are amenable to sequential tumor biopsies
Secondary
Characterize the pharmacokinetics of sirolimus in these patients
Determine the pharmacodynamic effects of sirolimus on tumor normal skin and normal oral mucosa of these patients
Correlate the pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects
Correlate the Akt signaling pathway with pharmacodynamic endpoints
Explore pharmacokinetic-pharmacodynamic and toxicodynamic relationships of sirolimus in these patients
Quantify the toxicity of sirolimus in these patients
Evaluate preliminarily the activity of sirolimus in these patients
OUTLINE This is a prospective dose-escalation study
Patients receive oral sirolimus once daily on days 1-28 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity The pharmacodynamic optimal dose is considered the dose at which 10 patients are treated without requiring further dose escalation
Patients undergo blood collection tumor tissue and normal skin biopsies and oral mucosal smears periodically for pharmacodynamic pharmacokinetic and biomarker correlative studies
After completion of study treatment patients are followed at 4 weeks
PROJECTED ACCRUAL A total of 30 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R21CA112919 | NIH | None | None |
| P30CA006973 | NIH | None | None |
| JHOC-J0402 | None | None | None |
| JHOC-04032602 | US NIH GrantContract | None | httpsreporternihgovquickSearchP30CA006973 |