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)
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
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
In both arms, courses repeat every 28 days in the absence of disease progression or
After completion of study therapy, patients are followed periodically for up to 3 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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)
Up to 8 weeks
Southwest Oncology Group
United States: Food and Drug Administration
|Presbyterian Hospital||Charlotte, North Carolina 28233-3549|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Fremont - Rideout Cancer Center||Marysville, California 95901|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|
|Southwest Oncology Group||San Antonio, Texas 78245|