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

This study has been terminated.
(Permanently Closed Due to Poor Accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00087295
First received: July 8, 2004
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Drug: Depsipeptide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: June 2004
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Depsipeptide
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

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087295

Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Daniel P. Petrylak, MD Herbert Irving Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00087295     History of Changes
Other Study ID Numbers: CDR0000373886, U10CA032102, S0400
Study First Received: July 8, 2004
Last Updated: October 31, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

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:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014