Ignite Creation Date:
2024-05-05 @ 6:32 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00499486
Status:
COMPLETED
Last Update Posted:
2016-10-19
First Post:
2007-07-10
Brief Title:
Sirolimus in Treating Patients With Advanced Pancreatic Cancer
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
Phase II Clinical Biological and Pharmacological Study of Rapamycin Rapamune Sirolimus in Patients With Advanced Pancreatic Cancer
Status:
COMPLETED
Status Verified Date:
2016-10
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 II trial is studying how well sirolimus works in treating patients with advanced pancreatic cancer
PURPOSE This phase II trial is studying how well sirolimus works in treating patients with advanced pancreatic cancer
Detailed Description:
OBJECTIVES
Primary
To determine the proportion of patients with previously treated advanced pancreatic cancer surviving at 6 months after treatment with single agent rapamycin
To evaluate the relationship between activation of the PI3AktmTORS6K signaling pathway in tumor tissues and rapamycin activity in this patient population
To characterize toxicity of rapamycin in this patient population
Secondary
To determine the response rate median time to treatment failure and median survival of patients with previously treated advanced pancreatic cancer who are treated with single agent rapamycin
To characterize the pharmacokinetics of rapamycin in this patient population
To explore pharmacogenomic variables that affect rapamycin pharmacokinetics and clinical activity in this patient population
To determine the pharmacodynamic effects of rapamycin on S6 kinase activation in PBMC normal skin and normal oral mucosa obtained from patients treated with the drug and its relationship with rapamycin pharmacokinetics and clinical effects
To explore biomarkers in tumor tissues that might be associated with rapamycin clinical effects
OUTLINE Patients receive oral sirolimus once daily on days 1-28 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Patients undergo blood normal skin and tumor tissue collection at baseline and periodically during study for pharmacological biological and genotyping studies Blood samples are analyzed by LCMSMS assay to assess rapamycin pharmacokinetics PKs during courses 1 and 2 and to determine baseline CYP3A4 activity Samples are also analyzed by genotyping studies to assess CYP3A4 polymorphisms Pharmacodynamic activity of rapamycin is assessed in peripheral blood mononuclear cells isolated from PK blood samples using a kinase assay to measure S6K activity Tumor tissue is collected from pretreatment tumor samples obtained at the time of diagnosis or surgery or by biopsy from patients for whom pre-study tumor specimens are not available Patients undergo skin biopsies at baseline and on day 1 of course 2 to obtain samples of normal skin Patients also undergo oral mucosa smears at baseline and weekly during course 1 Tumor tissue normal skin and oral mucosa samples are assessed by IHC staining of S6K and p-S6K and by RT-PCR for cyclin D1 and p27
Primary
To determine the proportion of patients with previously treated advanced pancreatic cancer surviving at 6 months after treatment with single agent rapamycin
To evaluate the relationship between activation of the PI3AktmTORS6K signaling pathway in tumor tissues and rapamycin activity in this patient population
To characterize toxicity of rapamycin in this patient population
Secondary
To determine the response rate median time to treatment failure and median survival of patients with previously treated advanced pancreatic cancer who are treated with single agent rapamycin
To characterize the pharmacokinetics of rapamycin in this patient population
To explore pharmacogenomic variables that affect rapamycin pharmacokinetics and clinical activity in this patient population
To determine the pharmacodynamic effects of rapamycin on S6 kinase activation in PBMC normal skin and normal oral mucosa obtained from patients treated with the drug and its relationship with rapamycin pharmacokinetics and clinical effects
To explore biomarkers in tumor tissues that might be associated with rapamycin clinical effects
OUTLINE Patients receive oral sirolimus once daily on days 1-28 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Patients undergo blood normal skin and tumor tissue collection at baseline and periodically during study for pharmacological biological and genotyping studies Blood samples are analyzed by LCMSMS assay to assess rapamycin pharmacokinetics PKs during courses 1 and 2 and to determine baseline CYP3A4 activity Samples are also analyzed by genotyping studies to assess CYP3A4 polymorphisms Pharmacodynamic activity of rapamycin is assessed in peripheral blood mononuclear cells isolated from PK blood samples using a kinase assay to measure S6K activity Tumor tissue is collected from pretreatment tumor samples obtained at the time of diagnosis or surgery or by biopsy from patients for whom pre-study tumor specimens are not available Patients undergo skin biopsies at baseline and on day 1 of course 2 to obtain samples of normal skin Patients also undergo oral mucosa smears at baseline and weekly during course 1 Tumor tissue normal skin and oral mucosa samples are assessed by IHC staining of S6K and p-S6K and by RT-PCR for cyclin D1 and p27
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 |
|---|---|---|---|
| JHOC-04-06-16-01 | US NIH GrantContract | None | httpsreporternihgovquickSearchP30CA006973 |
| P30CA006973 | NIH | None | None |
| JHOC-J0415 | None | None | None |