TOCOSOL(TM) Paclitaxel in Metastatic or Locally Advanced Unresectable Transitional Cell Carcinoma of the Urothelium

A Phase 2 Multicenter Evaluation of the Safety and Efficacy of TOCOSOL(TM) Paclitaxel (S-8184 Paclitaxel Injectable Emulsion) in Patients With Metastatic or Locally Advanced, Unresectable Transitional Cell Carcinoma of the Urothelium

Phase 2B, multicenter study evaluating the safety and efficacy of weekly TOCOSOL Paclitaxel in taxane-naive patients receiving second line chemotherapy for metastatic or locally advanced, unresectable transitional cell carcinoma of the urothelium

Inclusion Criteria:

• Histologic diagnosis of transitional cell carcinoma (TCC) of the urothelium including bladder, renal pelvis, ureter, or urethra
• Stage IV disease
• One and only one prior systemic cytotoxic chemotherapy regimen administered as adjuvant or neoadjuvant chemotherapy or to treat locally advanced or metastatic disease
• Adequate hematologic function (ANC >/= 1500 cells/mm3 & platelet count >/= 100,000/mm3)
• Serum creatinine </= 2.0 mg/dL
• Total bilirubin </= 1.5 mg/dL
• SGOT & SGPT </= 3 times upper limit of institutional normal values
• PT (INR) & PTT within institutional lab normal range
• Karnofsky performance status of 60-100%
• At least one unidimensionally measurable lesion, suitable for radiographic evaluation of disease response, consistent with RECIST criteria
• Signed IRB/EC approved Informed Consent
• Life expectancy of at least 12 weeks
• 18 years of age or older
• Fully recovered from any previous surgery
• Not pregnant and willing to use a medically effective form of contraception during periods of chemotherapy treatment (both males and and females)
• Agree not to take vitamin E supplementation while receiving study medication
• Willing to participate in requested follow-up evaluations
• Willing to permit treating physicians to provide information to Sonus regarding disease status and survival for 2 years after first dose of study drug

Exclusion Criteria:

• Prior taxane-containing chemotherapy including Taxol(R) (paclitaxel) or generic equivalent, or Taxotere(R) (docetaxel)
• Peripheral neuropathy NCI-CTC grade 2 or greater
• Wide-field radiation, cytotoxic chemotherapy or hormonal therapy within 4 weeks of first dose, or mitomycin or nitrosoureas within 6 weeks of first dose, of study drug
• An investigational agent within 4 weeks of first dose of study drug
• Concurrent anticonvulsants known to induce P450 isoenzymes
• Patients who are pregnant or lactating
• A history of carcinoma of another primary site (other than non-melanoma skin cancers or carcinoma-in-situ of the cervix) within the previous 5 years, unless metastatic disease has been biopsied and documented to be TCC
• Bone metastasis, effusions, ascites or elevated tumor markers as the only evidence of metastatic TCC
• Brain metastasis
• Active bowel obstruction
• Active, serious infection or other serious medical problems (other than TCC) likely to impair completion of the study protocol