S0353, Gemcitabine in Treating Patients With Recurrent Bladder Cancer That Has Not Responded to Previous Bacillus Calmette-Guerin

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine directly into the bladder may kill more tumor cells. PURPOSE: This phase II trial is studying how well gemcitabine works in treating patients with recurrent bladder cancer that has progressed despite previous Bacillus Calmette-Guerin (BCG).

Detailed Description
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OBJECTIVES: Determine the 8-12 week efficacy of intravesical gemcitabine, in terms of complete response rate, in patients with recurrent superficial transitional cell carcinoma of the bladder that have progressed despite prior intravesical Bacillus Calmette-Guerin (BCG). Determine the recurrence-free, worsening-free, progression-free, and overall survival of patients treated with this drug. Evaluate the toxicity of this drug in these patients. Correlate, preliminarily, expression levels of genes or genetic polymorphisms involved in the gemcitabine pathway and angiogenesis with clinical toxicity, response, and relapse-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. Induction therapy: Patients receive gemcitabine intravesically once a week for 6 weeks (weeks 1-6) in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response proceed to maintenance therapy at week 14. Maintenance therapy: Patients receive gemcitabine intravesically once in weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 25-45 patients will be accrued for this study within 6-12 months.

Official Title
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Phase II Study of Intravesical Gemcitabine in Patients With Superficial Bladder Cancer Who Have Progressed Despite Intravesical BCG

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed superficial transitional cell carcinoma (TCC) of the bladder meeting 1 of the following stage criteria: Stage T1, grade 2-3 Stage Tis Stage Ta, grade 3-4 or multifocal (> 2 lesions) Must have received and failed ≥ 2 courses of intravesical Bacillus Calmette-Guerin (BCG) (one 6-week course, plus one 3-week course, or fewer weeks if BCG was discontinued due to side effects) within the past 3 years Recurrent disease Must have had a transurethral resection of the bladder tumor (TURBT) or bladder biopsy within the past 60 days documenting tumor recurrence and tumor stage and grade TURBT or biopsy must have been performed ≥ 6 weeks after the completion of BCG and/or other immunotherapy treatment (or ≥ 14 days after completion of intravesical chemotherapy treatment) All visible tumor must have been resected at the time of the last biopsy No evidence of urethral or renal pelvis TCC by upper tract radiological imaging (e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2 years PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified 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 in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Prior intravesical interferon alfa allowed, alone or in combination with Bacillus Calmette-Guerin (BCG) Chemotherapy See Disease Characteristics No more than 1 course of intravesical chemotherapy (e.g., thiotepa, mitomycin, or doxorubicin) within the past year, defined as 6 or more weekly instillations, with or without monthly maintenance instillations No prior gemcitabine Endocrine therapy Not specified Radiotherapy No prior pelvic radiotherapy No concurrent radiotherapy to any other area of the body Surgery See Disease Characteristics Recovered from prior surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Intravesical Gemcitabine<br> | Drug: gemcitabine hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate at the End of Induction | Complete Response is defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology at the Week 8 - 12 cystoscopy | Week 8-12, then every 3 months for the first 2 years, and then every 6 months for the years 3-5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Measured from the day of registration to death due to any cause. Survival is censored at date of last contact. | 1 year | 
| Recurrence-free Survival (RFS) | Recurrence-free Survival is defined as time from registration to first instance of disease recurrence, or death due to any cause. | 1 year | 
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | Patients were assessed for adverse events weekly for 6 weeks and then every 4 weeks for 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent bladder cancer, stage 0 bladder cancer, stage I bladder cancer, transitional cell carcinoma of the bladder