Bevacizumab, Everolimus, and Erlotinib in Treating Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00276575|
Recruitment Status : Completed
First Posted : January 13, 2006
Last Update Posted : November 19, 2014
RATIONALE: 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. Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and everolimus may also block blood flow to the tumor. Giving everolimus and erlotinib together with bevacizumab may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of erlotinib and everolimus when given together with bevacizumab in treating patients with advanced solid tumors.
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Biological: bevacizumab Drug: erlotinib hydrochloride Drug: everolimus||Phase 1|
- Estimate the maximum tolerated dose (MTD)/recommended phase II regimen of everolimus and erlotinib hydrochloride when given with bevacizumab in patients with advanced solid tumors.
- Evaluate safety of bevacizumab, everolimus, and erlotinib hydrochloride in these patients.
- Describe the impact of this combination therapy on dermal wound angiogenesis and inhibition of vascular endothelial growth factor receptor 1 (VEGFR1), mTOR/p70S6K, and other related markers in granulation tissue.
- Evaluate clinical activity (partial response, complete response, or stable disease > 6 months) associated with this regimen.
OUTLINE: This is a dose-escalation study followed by a randomized study.
- Part 1: Patients receive bevacizumab IV on days 1 and 15 and oral everolimus and oral erlotinib hydrochloride* once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of patients receive escalating doses of everolimus or escalating doses of everolimus and erlotinib hydrochloride* until the maximum tolerated dose (MTD) is determined. Patients in part 2 of the study are treated at the MTD of everolimus and erlotinib hydrochloride.
NOTE: *The first cohort of patients receive bevacizumab and everolimus only until the MTD is determined, the subsequent cohorts of patients receive bevacizumab, everolimus, and erlotinib hydrochloride
Part 2: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral everolimus once daily beginning on day 1, oral erlotinib hydrochloride once daily beginning on day 15, and bevacizumab IV once every 2 weeks beginning on day 15. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral erlotinib hydrochloride once daily beginning on day 1, oral everolimus once daily beginning on day 15, and bevacizumab IV once every 2 weeks beginning on day 15. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Bevacizumab in Combination With Everolimus and Erlotinib in Advanced Cancer|
|Study Start Date :||March 2005|
|Actual Primary Completion Date :||October 2012|
|Actual Study Completion Date :||September 2014|
Experimental: Bevacizumab, Everolimus, and Erlotinib
Dose Level Dose Bevacizumab (mg/kg q2wks) Everolimus (mg daily) Erlotinib (mg daily) -1 5 5 ---
Drug: erlotinib hydrochloride
- Maximum Tolerated Dose [ Time Frame: Until study completion ]Its primary objective is to estimate the MTD/recommended phase II dose combination or regimen
- Safety [ Time Frame: Until study completion ]endpoints will be evaluated in an exploratory fashion
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00276575
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Herbert I. Hurwitz, MD||Duke Cancer Institute|