A Phase I Study of Bevacizumab in Combination With SU11248
Overview
- Phase
- Phase 1
- Intervention
- sunitinib malate
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Maximum tolerated dose (MTD) of bevacizumab in combination with sunitinib malate determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This phase I trial is studying the side effects and best dose of bevacizumab and sunitinib in treating patients with solid tumors. 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. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sunitinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with sunitinib may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of bevacizumab in combination with sunitinib malate (SU11248) in patients with solid tumors. SECONDARY OBJECTIVES: I. Evaluate the objective response rate, time to disease progression, and overall survival of these patients. OUTLINE: This is a multicenter, dose-escalation study. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bevacizumab and SU11248 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. At least 10 patients are treated at the MTD. After completion of study therapy, patients are followed for 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven metastatic/unresectable adrenocortical carcinoma or melanoma not amenable to curative surgical or radiation therapy.
- •Accrual closed as of 5/27/2009 to patients with renal cell carcinoma
- •No squamous cell histology
- •No histology in close proximity to a major blood vessel
- •No history of or known brain metastases, spinal cord compression, or carcinomatous meningitis
- •No new evidence of brain or leptomeningeal disease on screening CT scan or MRI
- •ECOG performance status (PS) 0-1 OR Karnofsky PS 60-100%
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- •Bilirubin ≤ 1.5 times ULN
- •Creatinine ≤ 1.5 times ULN
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (sunitinib malate, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Intervention: sunitinib malate
Treatment (sunitinib malate, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
Treatment (sunitinib malate, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Intervention: pharmacological study
Treatment (sunitinib malate, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) of bevacizumab in combination with sunitinib malate determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Time Frame: 42 days
Secondary Outcomes
- Objective response rate assessed by RECIST(Up to 5 years)
- Overall survival(Up to 5 years)
- Progression-free survival(Up to 5 years)