Glioblastoma Multiforme Clinical Trial
Official title:
A Phase 2 Study of TRC105 in Patients With Recurrent Glioblastoma (GBM)
Background:
- Glioblastoma is an aggressive type of brain cancer that often resists treatment. TRC105 is
an experimental drug that blocks the growth of new blood vessels. It is being studied for
possible use in treating different kinds of cancer. Researchers want to see if TRC105 can be
used to treat glioblastoma that has not responded to standard treatments.
Objectives:
- To test the safety and effectiveness of TRC105 in adults who have glioblastoma that has
not responded to standard treatments.
Eligibility:
- Individuals at least 18 years of age who have glioblastoma that has not responded to
standard treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine
samples will be collected. Imaging studies and other tests will be used to study the
tumor before the start of treatment.
- Participants will have 28-day (4-week) cycles of treatment.
- Participants will have TRC105 intravenously once a week. The first infusion will take
about 4 hours. The length of time needed for the infusion may be slowly reduced if it
is well tolerated.
- At the end of the first cycle (the first 4 weeks), the imaging studies will be repeated
before continuing TRC105.
- Participants will take TRC105 for as long as the tumor does not grow and the side
effects are not too severe. They will have imaging studies at the end of every cycle to
evaluate the tumor.
Background:
- TRC105 is an anti-angiogenic monoclonal antibody (mAb) that binds to CD105 (Endoglin),
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 glioblastoma
multiforme (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 (vascular endothelial growth factor ) 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).
Objectives:
Primary
- To determine the radiographic response rate for patients with recurrent GBM treated
with TRC105.
- To establish data regarding the anti-tumor activity of TRC105 in patients with GBM, as
determined by progression free survival.
Secondary
- 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
with TRC105.
- To examine the effect of TRC105 on vascular permeability as measured by percent change
from baseline in the forward contrast transfer rate (Ktrans) of dynamic
contrast-enhanced magnetic resonance imaging (DCE-MRI).
- To examine the effect of TRC105 on vascular perfusion as measured by percent change
from baseline in cerebral blood volume (CBV), cerebral blood flow (CBF), and mean
transit time (MTT) of dynamic susceptibility contrast magnetic resonance imaging
(DSC-MRI).
- To examine the effect of TRC105 on water diffusion as measured by percent change from
baseline in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of
diffusion magnetic resonance imaging (MRI).
- To examine the effect of TRC105 on tumor metabolism as measured by percent change from
baseline in fludeoxyglucose F18 injection (FDG) uptake of positron emission tomography
(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.
Eligibility:
-This is a phase II trial in patients with recurrent GBM who are VEGF therapy naive.
Design:
-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 magnetic resonance (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.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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