Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer

Urothelial cancer typically begins in the lining of the bladder, the balloon-shaped organ in
the pelvic area that stores urine. Urothelial cancer can also begin in the ureter (the tube
connecting the kidney and bladder), part of the kidney itself, or the urethra (the tube you
pass urine out of). Some Urothelial cancers remain confined to the lining, while in other
cases they spread to other areas. Treatment for these cancers varies greatly depending on
the stage of disease at the time of diagnosis. Study participants in this research study
will have a diagnosis of urothelial cancer that is advanced or has come back after prior
therapy.

There are two standard chemotherapeutic regimens for the management of this disease. One is
the combination of the drugs, methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC).
However the toxicities associated with this treatment regimen (side effects) is high.

The other is a combination of two drugs called Cisplatin and Gemcitabine. These drugs are
also known to destroy urothelial cancer cells, and are better tolerated by patients. All
study participants will receive both of these drugs.

Another anti-cancer drug called Cetuximab is known to delay or prevent tumor growth and in
some cases to lead to death of cancer cells by blocking certain cellular pathways that lead
to tumor development. This drug has been approved by the United States Food and Drug
Administration (FDA) for the treatment of colorectal cancer and for treatment of head and
neck cancers. The use of Cetuximab for the treatment of urothelial cancer is investigational
in this study.

The purpose of this study is to compare the safety and efficacy of Gemcitabine and Cisplatin
administered with or without the addition of Cetuximab in study participants with urothelial
cancer.

This is a randomized research study. Study participants will be randomized to receive either
gemcitabine and cisplatin alone or in combination with Cetuximab.

Inclusion Criteria:

- Study participants will be male or female at least 18 years of age

- Study participants will have a histologic/cytologic diagnosis of urothelial carcinoma
(transitional cell carcinoma; either pure or mixed histology) that is metastatic,
locally recurrent, or unresectable (T4bN0 or any T, N2030)

- Study participants must have measurable disease by radiologic imaging. Study
participants that have received previous radiation therapy, recovered from side
effects and have not had more than 25% of the bone marrow

- Study participants must have adequate bone marrow function

Exclusion Criteria:

- Study participants may not have received previous systemic chemotherapy for the
current stage of disease with the following exception: prior neoadjuvant or adjuvant
chemotherapy is allowed provided it has been at least 6 months since treatment with
non-cisplatin containing regimens and > 1 year since treatment with a cisplatin
containing regimen

- Study participants may not have received prior therapy targeting the EGFR pathway

- Study participants may not have a history or known spinal cord compression, or
carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease
on screening CT or MRI scan

- Study participants may not have known HIV due to the intense nature of the
chemotherapy in this trial

- Study subjects may not have a history of congestive heart failure (CHF), chronic
renal failure, active TIAs, recent (in the last 6 months) stroke, symptomatic
pulmonary embolism (PE), or myocardial infarction.

- Study participants with history of DVT or incidental or asymptomatic PE will be
eligible for the study as deemed appropriate by the treating physician provided they
continue prophylactic or full dose anticoagulation as per standards of care for the
specific event.

- Study participants must not have a prior grade 3 or 4 severe infusion reaction to
monoclonal antibodies

- Study participants may not be pregnant or breastfeeding

- Study participants may not receive concurrent treatment on another therapeutic
clinical trial.