S0306, Irinotecan in Treating Patients With Recurrent or Refractory Advanced Transitional Cell Cancer of the Urothelium Previously Treated With Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of irinotecan in treating patients who have recurrent or refractory advanced transitional cell cancer of the urothelium.

Detailed Description
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OBJECTIVES: Determine the probability of response (confirmed complete and partial response) to treatment with irinotecan in patients with recurrent or refractory advanced transitional cell carcinoma of the urothelium previously treated with platinum-based chemotherapy. Determine the qualitative and quantitative toxic effects of this drug in these patients. Determine the overall and progression-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to prior pelvic radiotherapy (yes vs no). Patients receive irinotecan IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. 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 within 5-10 months.

Official Title
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Phase II Study of Irinotecan in Patients With Advanced Transitional Cell Carcinoma of the Urothelium

Conditions
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Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Intervention / Treatment
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* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma (TCC) of the urothelium, including the bladder, renal pelvis, ureter, and urethra Stage T2-4, N0-3, M1 OR stage T2-4, N+, M0, unresectable disease The following additional histologic subtypes are eligible: Poorly differentiated TCC Predominant TCC with rare foci of squamous differentiation Predominant TCC with rare foci of adenocarcinoma The following histologic subtypes are ineligible: Adenocarcinoma Small cell carcinoma Sarcoma Squamous cell carcinoma Mixed adeno/squamous/transitional histology Incurable by surgery or radiotherapy Progressed or recurred after 1, and only 1, prior cisplatin- or carboplatin-containing systemic regimen for metastatic disease Measurable disease Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease No uncontrolled central nervous system (CNS) metastases CNS metastases that have responded to or stabilized after prior radiotherapy are allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,200/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) Aspartate aminotransferase (SGOT) less than 3 times ULN (5 times ULN if liver metastases are present) Renal Creatinine less than 2 times ULN Other Not pregnant or nursing Fertile patients must use effective contraception 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 that is currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics At least 28 days since prior chemotherapy No prior topoisomerase I inhibitors (e.g., irinotecan or topotecan) Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 28 days since prior radiotherapy to the pelvis Surgery Not specified Other Recovered from prior therapy Prior adjuvant therapy allowed At least 14 days since prior Hypericum perforatum (St. John's Wort) More than 7 days since prior phenytoin, phenobarbital, carbamazepine, or any other enzyme-inducing anticonvulsant drugs (EIACDs) No St. John's Wort during and for 7 days after study participation No concurrent EIACDs No concurrent medications that cause myelosuppression No concurrent medications that cause diarrhea Concurrent gabapentin or other non-EIACDs are allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Irinotecan | Drug: irinotecan hydrochloride<br>* Irinotecan will be given 250 mg/m^2 through intravenous (IV) for 90 minutes on day 1 for every 21 days until tumor progression or unacceptable toxicity or other reason for discontinuation occurs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of response (confirmed complete and partial response) |  | From date of registration to date of progression or death from any cause, whichever came first, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and grade of adverse events |  | From date of registration to date of progression or death from any cause, whichever came first, assessed up to 3 years | 
| Overall survival |  | From date of registration to date of progression or death from any cause, whichever came first, assessed up to 3 years | 
| Progression-free survival |  | From date of registration to date of progression or death from any cause, whichever came first, assessed up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent bladder cancer, stage IV bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, transitional cell carcinoma of the bladder, anterior urethral cancer, posterior urethral cancer, recurrent urethral cancer, urethral cancer associated with invasive bladder cancer