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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Intervention / Treatment
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* Drug: Depsipeptide


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Depsipeptide | Drug: Depsipeptide<br>* Depsipeptide wil be given 13 mg/m^2 through an intravenous (IV) over 4 hours on day 1, 8, and 15 for every 28 days (1 cycle = 28 days) until progression. Patients achieving a complete response (CR) will receive two additional cycles of treatment, and then be removed from protocol treatment.<br>* Other names: FK228;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of response (confirmed complete and partial) |  | From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years | 
| Overall survival |  | From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years | 
| Number and grade of adverse events |  | From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent bladder cancer, stage IV bladder cancer, transitional cell carcinoma of the bladder, metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, anterior urethral cancer, posterior urethral cancer, recurrent urethral cancer, urethral cancer associated with invasive bladder cancer