A Phase 2 Study of TRC105 in Patients With Recurrent Glioblastoma (GBM)
- TRC105 is an anti-angiogenic monoclonal antibody (mAb) that binds to CD105, a
transmembrane glycoprotein that is essential for angiogenesis, and expressed abundantly
on activated vascular endothelial cells (ECs). CD105 is a member of the transforming
growth factor-Beta (TGF-Beta) receptor superfamily, and modulates TGF-Beta signaling
leading to EC proliferation and migration.
- Immunohistochemistry studies reveal that CD105 is preferentially expressed in blood
vessels of tumor tissues as compared with normal mucosa. For patients with GBM,
increased expression of CD105 may correspond to worse survival times. Furthermore,
expression of CD105 is essential for neovascularization, and is upregulated in the
setting of VEGF inhibition.
- TRC105 binding to CD105 leads to inhibition of EC proliferation, neovascularization,
and induces cell death via apoptosis. TRC105 may also mediate antibody-dependent
cellular cytotoxicity (ADCC).
- To determine the radiographic response rate for patients with recurrent GBM treated
- To establish data regarding the anti-tumor activity of TRC105 in patients with GBM, as
determined by progression free survival.
- To obtain information regarding the safety of TRC105 in patients with recurrent GBM.
- To evaluate the health-related quality of life (HRQL) in patients while on treatment
- To examine the effect of TRC105 on vascular permeability as measured by percent change
from baseline in Ktrans of DCE-MRI.
- To examine the effect of TRC105 on vascular perfusion as measured by percent change
from baseline in CBV, CBF, and MTT of DSC-MRI.
- To examine the effect of TRC105 on water diffusion as measured by percent change from
baseline in ADC and FA of diffusion MRI.
- To examine the effect of TRC105 on tumor metabolism as measured by percent change from
baseline in FDG uptake of PET scan.
- To obtain preliminary data regarding how changes in serial FDG-PET scans and
physiological MRI correlate with radiographic response rates and with progression free
survival in patients treated with TRC105.
-This is a phase II trial in patients with recurrent GBM who are VEGF therapy naive.
-Prior to treatment start, patients will undergo a magnetic resonance imaging (MRI)
including MRI perfusion and diffusion scans, as well as an FDG-PET scan. Patients will then
receive TRC105 as a single agent (weekly dose of 10 mg/kg IV). A cycle will consist of 4
weeks of therapy. At the end of the first cycle, the MR imaging and FDG-PET scans will be
repeated before continuing treatment. Patients who are clinically and neurologically stable,
and who have radiographic stable or responding disease at the end of each cycle will
continue treatment with TRC105. MRI perfusion and diffusion will be repeated after the
completion of each cycle of therapy.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the radiographic response rate for patients with recurrent GBM treated with TRC105.
Joohee Sul, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|