Dasatinib in Combination With Bevacizumab to Treat Advanced Solid Tumors
- Bevacizumab inhibits blood vessel growth in cancer cells by blocking a growth factor called VEGF. Dasatinib inhibits the action of proteins called tyrosine kinases, which promote and stimulate blood vessel formation and cancer growth and spread.
- Using the two drugs in combination may provide a more effective cancer treatment than either drug used alone.
- Both drugs have been approved by the Food and Drug Administration for different cancer types, but their use in combination sis experimental.
- To determine the highest doses of the combination of dasatinib and bevacizumab that can be safely given to patients with different cancers and to find out what effects, good and bad, these drugs may have on the patient and the disease.
- Adult patients with an advanced solid tumor cancer that cannot be treated successfully with standard therapies.
- Patients in Group 1 receive dasatinib and bevacizumab together throughout the study. The dose is increased in successive groups of three to six patients until the optimum safe dose is determined. Patients take dasatinib by mouth once a day and receive bevacizumab as an infusion through a vein once every 2 weeks in 28-day treatment cycles.
- Patients in Group 2 are randomly assigned to receive either dasatinib or bevacizumab for cycle one, and then both drugs for all subsequent cycles. The drug doses are based on the optimum doses found in Group 1 patients.
- Patients have a physical examination and blood and urine tests every 2 weeks for cycles 1 and 2, and then every 4 weeks for the duration of treatment.
- Patients have CT or MRI scans or another imaging test such as ultrasound every 8 weeks to monitor the cancer's response to treatment.
- Tumor biopsies are obtained from patients in Group 2 before treatment, 2 weeks into the first treatment cycle, and 2 weeks into the second cycle.
- Dynamic, contrast-enhanced MRI (DCE-MRI) tests are done on patients in Group 2 before treatment, 2 weeks into the first cycle and 4 weeks into the second cycle. This MRI test uses a special non-radioactive dye that shows blood flow in a certain part of the body.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Dasatinib in Combination With Bevacizumab in Advanced Solid Tumors|
- Determine the safety and toxicity of the combination of dasatinib and bevacizumab in advanced solid tumors that have progressed on standard therapy.
- Determine preliminary evidence of efficacy of the combination of bevacizumab and dasatinib. Determine biochemical changes in the src-FAC and src-PLC-y and VEGF signal transduction pathways in tumor and stromal cells in response to treatment.
|Study Start Date:||October 2008|
Dasatinib is an inhibitor of SRC family kinases, BCR-ABL, c-KIT, EPHA2 and PDGF beta receptor.
Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (k(d) equal to 1.1nM).
This Phase I trial is open to patients with all solid tumors.
Determine the safety and toxicity of the combination of dasatinib and bevacizumab.
Determine biochemical changes in the src-FAK and src-PLC-. and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD, in a pilot fashion, if those changes are statistically significant.
Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective.
Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.
All patients enrolling in Group 2 must have at least one lesion amenable to biopsy.
ECOG performance status 0 or 1 and adequate organ and marrow function.
Group 1 will receive dasatinib and bevacizumab together at the start of study in a dose escalation fashion.
Group 2 will be randomized as to which agent they receive for cycle one. Cycles 2 and beyond are treated using both agents.
Tumor biopsies will be obtained from patients in Group 2 before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.
DCE-MRI studies will be obtained on patients in Group 2 before treatment, two weeks into monotherapy, four weeks into monotherapy, and two weeks into combinatorial therapy.
Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2, and then every 4 weeks.
Patients will be evaluated for response every 8 weeks using the RECIST criteria.
Approximately 48 patients will be needed to achieve the objectives of the trial.
|Contact: Nicole D. Houston, R.N.||(301) firstname.lastname@example.org|
|Contact: Elise C Kohn, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Elise C Kohn, M.D.||National Cancer Institute (NCI)|