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A Phase II Study of TRC105 in Adults With Advanced/Mestastic Urothelial Carcinoma

Phase 2
18 Years
Open (Enrolling)
Urothelial Carcinoma, Ureteral Neoplasms, Ureter Cancer, Neoplasm, Ureteral, Cancer of the Ureter

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Trial Information

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
14 months.

- 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,
or gemcitabine).


- 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
disease progression.

- 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.

Inclusion Criteria


- Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra,
ureter, or renal pelvis, with histological confirmation at the Laboratory of
Pathology of the NCI, NIH.

- Patients must have progressive metastatic disease. Progressive disease will be
defined as new or progressive lesions on cross-sectional imaging. Patients must have
at least:

- One measurable site of disease (according to RECIST criteria) that has not been
previously irradiated. If the patient has had previous radiation to the marker
lesion(s), there must be evidence of progression since the radiation.

- Or, appearance of one new bone lesion.

- Patients must have been previously treated, as defined by the following:

- Treatment with at least one prior cytotoxic agent (which must have included at least
one of the following: cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine),
administered in the perioperative or metastatic setting and may have been
administered sequentially (e.g., first-line treatment followed by second-line
treatment at time of progression) or as part of a single regimen.

- 18 years of age or older

- ECOG performance status of < 2 or Karnofsky Performance Status greater than or equal
to 60%

- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or
surgical procedure to NCI CTCAE grade less than or equal to 1 or baseline

- Adequate organ function as defined by the following criteria:

- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT])
and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) less
than or equal to 2.5 times the upper limit of normal (ULN); 5.0 times the ULN in
cases of liver metastases

- Total serum bilirubin less than or equal to 1.5 mg/dL (unless elevation from
Gilbert's disease or similar syndrome due to slow conjugation of bilirubin)

- Absolute neutrophil count (ANC) greater than or equal to 1000/microL

- Platelets greater than or equal to 100,000/microL

- Serum creatinine less than or equal to 2.0 mg/dl or calculated creatinine clearance
(CrCl) greater than or equal to 30 mL/min

- Hemoglobin > 9gm/dL

- PT, aPTT must be within normal range

- Patients on anticoagulants may be enrolled as long as the INR does not exceed 3.


- Receipt of an investigational agent within 4 weeks prior to first dose with TRC105

- Major surgery including open biopsy or systemic therapy < 4 weeks prior to first
dose with TRC105

- Radiation therapy (except small field) < 3 weeks prior to first dose with TRC105

- Small field radiation therapy < 2 weeks prior to first dose with TRC105

- Minor surgical procedures within 2 weeks

- Uncontrolled chronic hypertension (systolic > 140 or diastolic > 90mm Hg despite
optimal therapy)

- Brain metastasis, or leptomeningeal disease because of their poor prognosis and
because they often develop progressive neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events.

- Unstable angina, MI, symptomatic congestive heart failure, cerebrovascular accident,
transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG
within the past 6 months

- Cardiac arrhythmias of NCI CTCAE grade greater than or equal to 2 within the last

- Serious, non-healing wound, ulcer, or bone fracture

- Known active hepatitis

- Hemorrhage within 30 days of dosing or history of persistent gross hematuria

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
related illness

- History of hypersensitivity reaction to human or mouse antibody products

- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.:
hysterectomy) or be postmenopausal, or must agree to use effective contraception
during the study and for 3 months following last dose of TRC105. All female patients
of reproductive potential must have a negative pregnancy test (serum) within 7 days
prior to first dose. Male patients must be surgically sterile or must agree to use
effective contraception during the study and for 3 months following last dose of
TRC105. The definition of effective contraception will be based on the judgment of
the Principal Investigator or a designated associate.

- Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the Investigator would make the patient inappropriate for entry
into this study

- History of peptic ulcer disease, unless a subsequent endoscopy has confirmed complete
resolution of the ulcer

- History of acquired or inherited hypocoagulopathies (bleeding risk), including but
not limited to hereditary hemorrhagic telangiectasis.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To measure PFS of TRC105 as determined by RECIST.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Andrea B Apolo, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

March 2011

Completion Date:

March 2015

Related Keywords:

  • Urothelial Carcinoma
  • Ureteral Neoplasms
  • Ureter Cancer
  • Neoplasm, Ureteral
  • Cancer of the Ureter
  • Progression-Free Survival
  • Carcinoma of the Bladder
  • Cancer of the Renal Pelvis
  • Ureter Cancer
  • Survival
  • Bladder Cancer
  • Renal Pelvis Cancer
  • Urothelial Cancer
  • Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell
  • Ureteral Neoplasms



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