Dasatinib and Bevacizumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery
| Status: | Archived |
|---|---|
| Conditions: | Breast Cancer, Lung Cancer, Prostate Cancer, Skin Cancer, Ovarian Cancer, Cancer, Cancer, Kidney Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | July 2008 |
A Phase I Study of Dasatinib in Combination With Bevacizumab in Advanced Solid Tumors
RATIONALE: Dasatinib 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 may
also stop the growth of solid tumors by blocking blood flow to the tumor. Giving dasatinib
together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib given
together with bevacizumab in treating patients with solid tumor that is metastatic or cannot
be removed by surgery.
OBJECTIVES:
Primary
- To describe the safety and toxicity of the combination of dasatinib and bevacizumab in
patients with advanced solid tumors that have progressed on standard therapy.
- To find the maximum tolerated dose or recommended phase II dose of this combination.
- To describe the biochemical changes in the Src-FAK, Src-PLC-γ, and VEGF signal
transduction pathways in tumor and stromal cells in response to treatment. (Group 2)
Secondary
- To determine, preliminarily, the efficacy of this regimen.
- To evaluate correlations between pathway alteration and clinical events.
- To evaluate correlations between clinical outcomes and changes in VEGF and other
angiogenic cytokines in plasma and circulating endothelial cells.
- To evaluate the application of dynamic contrast-enhanced MRI in determining early
changes in tumor vascularity during treatment.
OUTLINE: This is a dose-escalation study of dasatinib and bevacizumab (group 1) followed by
a randomized study (group 2).
- Group 1: Patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV
over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
- Group 2: Patients receive dasatinib and bevacizumab at the maximum tolerated dose
determined in group 1. Patients are randomized to 1 of 2 treatment arms.
- Arm I: In course 1, patients receive oral dasatinib alone once daily on days 1-28.
Beginning in course 2 and for all subsequent courses, patients receive oral
dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1
and 15. Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.
- Arm II: In course 1, patients receive bevacizumab IV over 30-90 minutes on days 1
and 15. Beginning in course 2 and for all subsequent courses, patients receive
oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on
days 1 and 15. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.
Patients in group 2 undergo tumor biopsies and dynamic contrast-enhanced MRI at baseline,
after 2 weeks of single-agent therapy, and after ≥ 2 weeks of combined therapy to examine
biochemical effects of treatment and to evaluate changes in vascularity and quality of index
lesions. Blood samples are also collected from these patients and archived for future
studies, including cytokine and invasion marker analysis and circulating endothelial cell
analysis.
After completion of study therapy, patients are followed for 4 weeks.
We found this trial at
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National Cancer Institute (NCI) The National Cancer Institute (NCI) is part of the National Institutes...
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