Sirolimus and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Recruitment status was Recruiting
|First Received Date ICMJE||April 25, 2007|
|Last Updated Date||June 21, 2011|
|Start Date ICMJE||January 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00467194 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Sirolimus and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery|
|Official Title ICMJE||A Phase I Study of Rapamycin in Combination With Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma|
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.
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 Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||Liver Cancer|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||41|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
PRIOR CONCURRENT THERAPY:
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Not Provided|
|Location Countries ICMJE||Singapore|
|NCT Number ICMJE||NCT00467194|
|Other Study ID Numbers ICMJE||CDR0000540163, SINGAPORE-06-17-HEP|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Centre, Singapore|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Cancer Institute (NCI)|
|Verification Date||September 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP