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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00087295
Recruitment Status : Terminated (Permanently Closed Due to Poor Accrual)
First Posted : July 12, 2004
Last Update Posted : November 2, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer Drug: Depsipeptide Phase 2

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2004
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Arm Intervention/treatment
Experimental: Treatment
Drug: Depsipeptide
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.
Other Names:
  • FR901228
  • FK228

Primary Outcome Measures :
  1. Probability of response (confirmed complete and partial) [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ]
  2. Overall survival [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ]
  3. Number and grade of adverse events [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 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 (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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00087295

Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
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Study Chair: Daniel P. Petrylak, MD Herbert Irving Comprehensive Cancer Center

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Responsible Party: Southwest Oncology Group Identifier: NCT00087295    
Other Study ID Numbers: CDR0000373886
U10CA032102 ( U.S. NIH Grant/Contract )
S0400 ( Other Identifier: SWOG )
First Posted: July 12, 2004    Key Record Dates
Last Update Posted: November 2, 2012
Last Verified: October 2012
Keywords provided by Southwest Oncology Group:
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
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urethral Diseases
Kidney Diseases
Ureteral Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents