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

SWOG Cancer Research Network

Status and phase

Terminated

Phase 2

Conditions

Transitional Cell Cancer of the Renal Pelvis and Ureter

Bladder Cancer

Urethral Cancer

Treatments

Drug: Depsipeptide

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00087295

CDR0000373886

S0400 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

6 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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