A Phase II Study of Depsipeptide (NSC-630176) In Patients With Advanced Transitional Cell Carcinoma Of The Urinary Tract Who Have Progressed After Receiving One Prior Chemotherapy Regimen For Advanced Disease

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed transitional cell carcinoma of the urothelium (bladder,
renal pelvis, ureter, or urethra)

- Metastatic disease

- Node-positive, non-metastatic disease that is unresectable is allowed

- Poorly differentiated transitional cell carcinoma OR predominant transitional
cell carcinoma with rare foci of squamous differentiation or rare foci of
adenocarcinoma allowed

- The following histologic types are not allowed:

- Adenocarcinoma

- Small cell carcinoma

- Sarcoma

- Squamous cell carcinoma

- Mixed adeno/squamous/transitional histology

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques
OR ≥ 1 cm by spiral CT scan

- Soft tissue disease irradiated within the past 2 months is not considered
measurable

- Disease progression or recurrence after 1, and only 1, prior systemic chemotherapy
regimen that included cisplatin or carboplatin for metastatic disease

- Not curable by surgery or radiotherapy

- No known brain metastases

PATIENT CHARACTERISTICS:

Age

- Not specified

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- White blood cell (WBC) count ≥ 3,000/mm^3

Hepatic

- Aspartate aminotransferase (SGOT) / alanine aminotransferase (SGPT) ≤ 2.5 times upper
limit of normal (ULN)

- Bilirubin normal

Renal

- Creatinine ≤ 2 times ULN

Cardiovascular

- Corrected QT interval (QTc) < 500 msec

- Left ventricular ejection fraction (LVEF) > 40% by Multi Gated Acquisition Scan
(MUGA)

- No New York Heart Association class III or IV congestive heart failure

- No myocardial infarction within the past year

- No uncontrolled dysrhythmias

- No poorly controlled angina

- No serious ventricular arrhythmia (ventricular tachycardia or ventricular
fibrillation ≥ 3 beats in a row)

- No left ventricular hypertrophy on EKG

- No other significant cardiac disease

Other

- Potassium ≥ 4 mmol/L

- Magnesium ≥ 2 mg/dL

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No prior allergic reaction to compounds of similar chemical or biological composition
to FR901228 (depsipeptide)

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy

Chemotherapy

- See Disease Characteristics

- At least 28 days since prior chemotherapy

- No prior FR901228 (depsipeptide)

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy

Radiotherapy

- See Disease Characteristics

- More than 28 days since prior radiotherapy

- No concurrent radiotherapy

Surgery

- More than 28 days since prior surgery

Other

- Recovered from all prior therapy

- More than 28 days since prior intravesical therapy

- No concurrent hydrochlorothiazide

- No concurrent agent that causes QTc prolongation

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational histone deacetylase inhibitor agents or drugs
(e.g., sodium valproate)

- No other concurrent anticancer therapy