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

Sponsor

Southwest Oncology Group (Other)

Overall Status

Terminated

CT.gov ID

NCT00087295

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

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 :

Jun 1, 2004

Actual Primary Completion Date :

Apr 1, 2006

Actual Study Completion Date :

Apr 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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