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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

Phase 2
Not Enrolling
Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

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Trial Information

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


- 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

- 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.

Inclusion Criteria


- 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

- 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



- Not specified

Performance status

- Zubrod 0-2

Life expectancy

- Not specified


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

- Platelet count ≥ 100,000/mm^3

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


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

- Bilirubin normal


- Creatinine ≤ 2 times ULN


- Corrected QT interval (QTc) < 500 msec

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

- 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


- 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


Biologic therapy

- No concurrent immunotherapy


- See Disease Characteristics

- At least 28 days since prior chemotherapy

- No prior FR901228 (depsipeptide)

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy


- See Disease Characteristics

- More than 28 days since prior radiotherapy

- No concurrent radiotherapy


- More than 28 days since prior surgery


- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Probability of response (confirmed complete and partial)

Outcome Time Frame:

From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years

Safety Issue:


Principal Investigator

Daniel P. Petrylak, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Herbert Irving Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

June 2004

Completion Date:

April 2006

Related Keywords:

  • Bladder Cancer
  • Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Urethral Cancer
  • 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
  • Urinary Bladder Neoplasms
  • Carcinoma, Transitional Cell
  • Urethral Neoplasms
  • Kidney Neoplasms
  • Ureteral Neoplasms