S0400, FR901228 in Treating Patients With Advanced Cancer of the Urothelium

RATIONALE: Drugs used in chemotherapy, such as FR901228 (depsipeptide), work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with advanced cancer of the urothelium that has progressed or recurred after receiving one chemotherapy regimen.

OBJECTIVES:

* Determine the response (confirmed complete and partial) in patients with advanced transitional cell carcinoma of the urothelium that has progressed after prior chemotherapy when treated with FR901228 (depsipeptide) .
* Determine progression-free and overall survival of patients treated with this drug.
* Determine the qualitative and quantitative toxic effects of this drug in these patients.
* Determine, preliminarily, the effects of this drug on reversing tumor promoter gene methylation in these patients.
* Correlate, preliminarily, tumor DNA in plasma with response or outcome in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response receive 2 additional courses of treatment.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study.

Eligibility 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