Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2026-01-02 @ 11:17 PM
Study NCT ID:
NCT00467194
Status:
COMPLETED
Last Update Posted:
2013-06-17
First Post:
2007-04-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Sirolimus and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Sponsor:
National Cancer Centre, Singapore
Organization:
Study Overview
Official Title:
A Phase I Study of Rapamycin in Combination With Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma
Status:
COMPLETED
Status Verified Date:
2013-06
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. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and sirolimus may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving sirolimus together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus when given together with bevacizumab in treating patients with liver cancer that cannot be removed by surgery.
PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus when given together with bevacizumab in treating patients with liver cancer that cannot be removed by surgery.
Detailed Description:
OBJECTIVES:
Primary
* Determine the maximum tolerated dose of sirolimus used in combination with bevacizumab in patients with unresectable hepatocellular carcinoma.
* Determine the toxicity profile of this regimen in these patients.
Secondary
* Determine the clinical activity of this regimen in these patients.
* Determine the pharmacokinetics of sirolimus in these patients.
* Determine the biologically active dose range of sirolimus in these patients.
* Correlate phosphorylated p70S6K activity with clinical response in patients treated with this regimen.
* Correlate PTEN, 4EBP-1, phosphorylated p70S6K, CD31, and vascular endothelial growth factor expression with clinical response in patients treated with this regimen.
* Correlate the degree of angiogenesis (as measured by DCE-CT scan) with drug levels and clinical response.
OUTLINE: This is a dose-escalation study of sirolimus.
Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks and oral sirolimus once daily. Treatment continues for up to 6 months 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. Six additional patients receive treatment at the MTD.
Blood samples are collected from healthy participants to measure p70S6 kinase activity. Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and p70S6K activity assessment. Samples are also analyzed by high-performance liquid chromatography and tandem mass spectrophotometry to determine peak drug concentrations. Patients without archived tumor samples undergo tumor tissue biopsy at baseline. Samples are analyzed for PTEN, 4E-BP1, vascular endothelial growth factor, epidermal growth factor, p70S6K, and CD31 by immunohistochemistry. Patients also undergo DCE-CT scan at baseline and on day 29 to assess angiogenesis.
After completion of study treatment, patients are followed for 52 weeks.
PROJECTED ACCRUAL: A total of 36 patients and 5 healthy participants will be accrued for this study.
Primary
* Determine the maximum tolerated dose of sirolimus used in combination with bevacizumab in patients with unresectable hepatocellular carcinoma.
* Determine the toxicity profile of this regimen in these patients.
Secondary
* Determine the clinical activity of this regimen in these patients.
* Determine the pharmacokinetics of sirolimus in these patients.
* Determine the biologically active dose range of sirolimus in these patients.
* Correlate phosphorylated p70S6K activity with clinical response in patients treated with this regimen.
* Correlate PTEN, 4EBP-1, phosphorylated p70S6K, CD31, and vascular endothelial growth factor expression with clinical response in patients treated with this regimen.
* Correlate the degree of angiogenesis (as measured by DCE-CT scan) with drug levels and clinical response.
OUTLINE: This is a dose-escalation study of sirolimus.
Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks and oral sirolimus once daily. Treatment continues for up to 6 months 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. Six additional patients receive treatment at the MTD.
Blood samples are collected from healthy participants to measure p70S6 kinase activity. Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and p70S6K activity assessment. Samples are also analyzed by high-performance liquid chromatography and tandem mass spectrophotometry to determine peak drug concentrations. Patients without archived tumor samples undergo tumor tissue biopsy at baseline. Samples are analyzed for PTEN, 4E-BP1, vascular endothelial growth factor, epidermal growth factor, p70S6K, and CD31 by immunohistochemistry. Patients also undergo DCE-CT scan at baseline and on day 29 to assess angiogenesis.
After completion of study treatment, patients are followed for 52 weeks.
PROJECTED ACCRUAL: A total of 36 patients and 5 healthy participants 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 ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| SINGAPORE-06-17-HEP | None | None | View |