A Phase II Study of TRC105 in Adults With Advanced/Mestastic Urothelial Carcinoma
- In the United States, urothelial carcinoma (UC) of the bladder is the 4th most common
malignancy in men and the 9th most common in women with an estimated 70,980 new cases
and 14,330 deaths in the year 2009. Although it is chemosensitive with response
proportions of over 50% with conventional cytotoxic regimens, the response durations
are short and the median survival of patients with metastatic disease is approximately
- TRC105 is a genetically engineered human/murine chimeric monoclonal antibody that
inhibits angiogenesis and tumor growth via endothelial cell growth inhibition and
apoptosis. TRC105 is directed against human CD105 (endoglin), an angiogenic membrane
protein that is highly expressed on proliferating vasculature in solid tumors and
up-regulated following anti-VEGF therapy. Clinical studies in bladder cancer with
anti-angiogenic agents have shown anti-tumor activity.
- TRC105 targets a unique mechanism for tumor angiogenesis, through modification of CD105
signaling. In patients with advanced bladder cancer that have progressed through
standard chemotherapy and have no further life prolonging therapeutic options, use of
this novel angiogenesis inhibitor may improve outcomes.
- To measure PFS of TRC105 as determined by RECIST v1.1
- To determine the safety and toxicity of TRC105 in this patient population.
- In addition, in a preliminary fashion, response rate and overall survival of patients
with metastatic urothelial carcinoma of the bladder treated with TRC105 will be
- Adults with progressive advanced/metastatic urothelial carcinoma that have progressed
despite treatment with prior cytotoxic chemotherapy.
- Subjects must have received at least one prior cytotoxic agent (which must have
included at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel,
- TRC105 will be administered at a dose of 15mg/kg intravenously every two weeks, on days
1 and 15 of each 28 day cycle.
- Patients may continue on study as long as they are tolerating therapy and are free of
- The study will be conducted as a two-stage optimal design (Simon 1989). With alpha=0.10
and beta=0.10 as acceptable error probabilities, the trial will target 30% as the
desirable proportion of patients who are still without progression by radiographic
criteria at approximately 6 months (p1=0.30), and will be considered inadequate if only
a fraction consistent with 10% are without progression by the same evaluation time
(p0=0.10). Initially 12 patients will be enrolled and followed for progression. If 2 or
more of the first 12 patients reach 6 months without progression, then enrollment will
continue until a total of 35 evaluable patients (37 total patients to allow for a small
number of inevaluable patients) have been entered.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To measure PFS of TRC105 as determined by RECIST.
Andrea B Apolo, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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