The purpose of this research study is to determine whether the investigational drug cetuximab, (Erbitux) alone or with paclitaxel (Taxol) can stabilize the growth of urothelial cancer.

This research study is being done to find out if cetuximab, alone or with paclitaxel will slow the growth of urothelial cancers. Cetuximab is an antibody that blocks a protein called epidermal growth factor receptor (EGFR). EGFR sits on the outside of tumor cells and controls tumor cell growth. This agent has been looked at alone and with other chemotherapy drugs including paclitaxel. It has been found to be safe and can shrink other types of cancer.

This research study is also being done to find out if cetuximab, alone or with paclitaxel shrinks urothelial tumors. If it extends the time the tumors shrink. If it helps people live longer.

The purpose of this research study is to find out what effects (good and bad) these treatments have on you and your cancer. We do not know if you will benefit from this research study. It is possible that your condition will get better, but it is also possible that there will be no effect on your condition or that your condition will get worse. We can use what we learn from this research study to help other people with the same disease.

Inclusion Criteria:

• Histologically confirmed carcinoma of the urothelium (bladder,renal pelvis, ureter)
• Measurable disease by RECIST
• Patients who received only one prior systemic non-taxane regimen for urothelial cancer. May have received this in the adjuvant or neoadjuvant setting or for advanced disease.
• Signed IRB approved consent
• Must have tissue available for EGFR assessment and additional correlative studies
• ECOG PS 0-2
• 18 years of age or older
• Not of child bearing potential or negative pregnancy test within 7 days of treatment
• ANC greater than or equal to 1,500/ul
• Platelets greater than or equal to 100,00/ul
• Creatinine less than or equal to 2x institutional ULN or create. clearance greater than or equal to 30, bilirubin less than or equal to 1.5x ULN, AST&ALT less than or equal to 5x ULN

Exclusion Criteria:

• Received more than one prior regimen for advanced disease
• Prior radiation to more than 30% of marrow containing skeleton
• Prior therapy that specifically and directly targets the EGFR pathway
• Prior severe infusion reaction to a monoclonal antibody, pre-existing neuropathy greater than or equal to grade 2
• Prior reaction to Cremophor EL
• Known acute hepatitis B or C or known HIV
• Active or uncontrolled infection
• Significant history of uncontrolled cardiac disease
• Any concurrent chemotherapy not indicated in this study; or
• Any other investigational agents