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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00087295
• Other study ID #: CDR0000373886
• Secondary ID: U10CA032102S0400
• Status: Terminated
• Phase: Phase 2
• First received: July 8, 2004
• Last updated: October 31, 2012
• Start date: June 2004
• Est. completion date: April 2006

Study information

• Verified date: October 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 2006
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Progression-free survival		From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years	No
Secondary	Overall survival		From date of registration to progression or death from any cause, whichever came first, assessed up to 3 years	No
Secondary	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	Yes