A Phase I/II Study of E7389 Halichondrin B Analog (NSC # 707389; IND # 64395) in Metastatic Urothelial Tract Cancer and Renal Insufficiency

Inclusion Criteria:

- Locally advanced or metastatic disease that is not amenable to surgical treatment

- No brain metastasis that is unstable (i.e., presenting with neurologic symptoms that
progress or require increasing doses of steroids within a 4-week period) or is
untreated (i.e., not radiated)

- Life expectancy > 6 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled intercurrent illness including, but not limited to, any of the
following: ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social
situations that would limit study compliance

- No more than 2 prior lines of therapy (for patients enrolled in phase I); more than 6
months since prior chemotherapy in the adjuvant setting* [Note: *for patients
enrolled at dose level 3 of phase I and all of phase II]

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent prophylactic granulocyte or platelet colony-stimulating factors

- Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1
dimension as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
(for patients enrolled in phase II or dose level 3 of phase I)

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9 g/dL

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- AST and ALT =< 2.5 times ULN

- Patients must have either (a) normal kidney function (i.e. creatinine =< 1.5 X ULN OR
calculated creatinine clearance >= 60 mL/min by the modified Cockcroft and Gault
Formula - OR a creatinine clearance >= 60 mL/min obtained from a 24-hour urine
collection) or (b) moderate or severe renal dysfunction (i.e. creatinine clearance <
60 mL/min and >= 20 mL/min)

- Patients with symptomatic uremia, uncontrolled edema or unstable serum
electrolytes should not enter the trial until such time as they have been
stabilized - such patients should be discussed with the Principal Investigator

- Histologically or cytologically confirmed urothelial tract carcinoma

- ECOG performance status (PS) 0-2 or Karnofsky PS 70-100%

- No HIV-positive patients on combination antiretroviral therapy or with CD4+ count ≤
500/mm³

- No concurrent dialysis