A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer
I. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in
combination with TRC105 (anti-endoglin monoclonal antibody TRC105).
I. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the
combination compared to single agent bevacizumab.
I. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta
receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth
factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order
to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular
endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether
exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.
II. A primary goal of tissue analysis will be to generate preliminary data to correlate
levels of CD105, TGFBR2, ACVRL1 and TGFBR1 in tissue with response to bevacizumab in
combination with anti-endoglin monoclonal antibody TRC105 compared to bevacizumab alone.
III. To compare the soluble CD105 levels at baseline and after treatment between the group
receiving bevacizumab alone and the group receiving bevacizumab in combination with
anti-endoglin monoclonal antibody TRC105.
IV. To compare TGFBR2 levels at baseline and after treatment between the group receiving
bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin
monoclonal antibody TRC105.
V. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient
population using parylene membrane filter technology, and whether changes in CTC counts and
CD105 expression on CTCs during therapy correspond to imaging and clinical response.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.
ARM II: Patients receive bevacizumab as in arm 1 and anti-endoglin monoclonal antibody
TRC105 IV over 1-4 hours on days 1, 8, 15, and 22.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study therapy, patients are followed for 4 weeks.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS)
Planning is based on the supposition of 12-week PFS of 61% on the control arm and 78% on the combination arm.
The duration of time from start of treatment to time of progression or death, assessed at 12 weeks
Beckman Research Institute
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|City of Hope||Duarte, California 91010|
|Wayne State University||Detroit, Michigan 48202|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|Metro-Minnesota CCOP||St. Louis Park, Minnesota|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|M D Anderson Cancer Center||Houston, Texas 77030|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|City of Hope Medical Group Inc||Pasadena, California 91105|
|University of Miami Miller School of Medicine-Sylvester Cancer Center||Miami, Florida 33136|
|University of Colorado at Denver Health Sciences Center||Denver, Colorado 80045|