Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy and surgery may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination chemotherapy in treating patients who have stage II or stage III bladder cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Evaluate the safety and tolerability of induction chemoradiotherapy with paclitaxel and cisplatin followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy in patients with stage II or III muscle invasive carcinoma of the bladder previously treated with transurethral tumor resection. Evaluate the efficacy of transurethral tumor resection and induction chemoradiotherapy in achieving a complete response in this patient population. Assess the value of tumor parameters as prognostic factors for initial tumor response and recurrence-free survival in this patient population. OUTLINE: Four to six weeks after prior transurethral resection, patients receive induction therapy comprising paclitaxel IV over 1 hour on days 1, 8, and 15, cisplatin IV over 1 hour on days 1, 2, 8, 9, 15, and 16, and radiotherapy twice daily on days 1-5, 8-12, and 17. Four weeks after induction therapy, patients undergo urologic evaluation. At 1-2 weeks after evaluation, patients with complete response receive consolidation therapy comprising paclitaxel IV over 1 hour on days 1 and 8, cisplatin IV over 1 hour on days 1, 2, 8, and 9, and radiotherapy twice daily on days 1-5 and 8-10. Patients with poor tumor response undergo a cystectomy. At 12 weeks postconsolidation therapy or 8 weeks post radical cystectomy, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30-60 minutes followed by cisplatin IV over 1 hour every 3 weeks. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 3 years.

Official Title
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A Phase I/II Trial in Patients With Muscle-Invading Bladder Cancer of Transurethral Surgery Plus Taxol, Cisplatin and Bid Irradiation Followed by Either Selective Bladder Preservation or Radical Cystectomy and Adjuvant Chemotherapy

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage II or III (T2-4a, Nx or N0, M0) primary carcinoma of the bladder with muscle invasion Resectable disease Prostatic urethral involvement with transitional cell carcinoma allowed, if completely resected and no evidence of stromal invasion No tumor-related hydronephrosis Positive lymph node must be evaluated by lymphadenectomy or percutaneous needle biopsy No nodal metastases No distant metastases No more than 6 weeks since prior transurethral resection of the bladder tumor Functioning bladder PATIENT CHARACTERISTICS: Age: Adult Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Hemoglobin at least 10 g/dL White blood cell (WBC) count of at least 4,000/mm^3 Absolute neutrophil count at least 1,800/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Other: No other prior or concurrent malignancy within the past 5 years except curatively treated nonmelanoma skin cancer, stage I prostate cancer, or carcinoma in situ of the cervix Not pregnant Negative pregnancy test Fertile patients must use effective contraception Medically operable PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior pelvic radiotherapy Surgery: See Disease Characteristics Other: No concurrent potential nephrotoxic or ototoxic drugs (e.g., aminoglycosides)

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: Arm 1<br>Transurethral surgery with chemotherapy and radiation therapy followed by either selective bladder preservation or radical cystectomy followed by adjuvant chemotherapy. | Drug: cisplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion and safety of induction chemo-radiotherapy followed by definitive local therapy of either radical cystectomy or consolidation TCI, followed by four cycles of outpatient adjuvant gemcitabine-cisplatin chemotherapy. | Completion and safety of induction chemo-radiotherapy (cisplatin, paclitaxel and irradiation [TCI]) followed by definitive local therapy of either radical cystectomy (for patients for whom the initial tumor is not a complete response) or consolidation TCI (for patients for whom the initial tumor has cleared), followed by four cycles of outpatient adjuvant gemcitabine-cisplatin chemotherapy. | From start to end of all protocol therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response after TCI induction |  | From start to end of all protocol therapy | 
| Completion and safety of the four cycles of gemcitabine-cisplatin chemotherapy |  | From start to end of all protocol therapy | 
| Invasive local treatment failure |  | From start of protocol treatment to date of local failure. Analysis occurs after all patients have copmleted treatment. | 
| Distant metastasis |  | From start of protocol treatment to date of distant metastasis | 
| To examine the value of tumor histopathology, molecular genetics and DNA flow cytometric parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival. |  | From the start of protocol treatment to the date the last patient has completed treatment. Analysis occurs after all patients have completed treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II bladder cancer, stage III bladder cancer