Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer
This phase I/randomized phase II trial is studying the side effects and best dose of bevacizumab and to see how well it works when given together with or without MEDI-522 in treating patients with unresectable or metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and MEDI-522, 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 MEDI-522 may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without MEDI-522 in treating kidney cancer.
Recurrent Renal Cell Cancer
Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I and a Randomized Phase II Study of Maximal Angiogenic Blockade in Advanced Renal Carcinoma: Bevacizumab (NSC-704865) With or Without MEDI-522 (NSC-719850)|
- Maximum tolerated dose of bevacizumab , based on incidence of DLT graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I) [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]
- Progression-free survival (Phase II) [ Time Frame: From date of registration to date of first observation of progressive disease, systemic deterioration, or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
- Incidence of adverse events, graded according to NCI CTCAE version 3.0 (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
- Overall survival (Phase II) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
- Response rate according to RECIST, including confirmed and unconfirmed complete and partial responses (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Phase II Arm I
Patients receive bevacizumab (10mg/kg) IV over 30-90 minutes on days 1 and 15.
Active Comparator: Phase II Arm II
Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.
Other Names:Biological: bevacizumab
I. To assess the appropriate dose of bevacizumab when administered with humanized monoclonal antibody MEDI-522 in patients with unresectable or metastatic renal cell carcinoma previously treated with sunitinib malate or sorafenib tosylate. (Phase I) II. To compare the progression-free survival of these patients treated with bevacizumab with versus without humanized monoclonal antibody MEDI-522. (Phase II) III. To evaluate the qualitative and quantitative toxicities of bevacizumab and humanized monoclonal antibody MEDI-522 in these patients. (Phase II) IV. To estimate overall survival and RECIST response rate (i.e., confirmed and unconfirmed, complete and partial responses) in both treatment arms. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of bevacizumab followed by a randomized phase II study.
PHASE I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and humanized monoclonal antibody MEDI-522 IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until the recommended phase II dose (RPTD) of bevacizumab is determined.
PHASE II: Patients are stratified according to the number of prior treatment regimens for renal cell carcinoma (1 vs 2) and whether there is a clear cell component (yes vs no). Patients are randomized to 1 of 2 treatment arms:
ARM I: Patients receive bevacizumab (10 mg/kg) IV over 30-90 minutes on days 1 and 15.
ARM II: Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8 mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.
In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically for up to 3 years.
|United States, California|
|Fremont - Rideout Cancer Center|
|Marysville, California, United States, 95901|
|UC Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Michigan|
|University of Michigan University Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, North Carolina|
|Charlotte, North Carolina, United States, 28204|
|United States, Texas|
|Southwest Oncology Group|
|San Antonio, Texas, United States, 78245|
|Principal Investigator:||Christopher Ryan||Southwest Oncology Group|