Gemcitabine, Cisplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of gemcitabine when given together with cisplatin and radiation therapy and to see how well they work in treating patients with stage II or stage III bladder cancer.

Detailed Description
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OBJECTIVES: Primary Determine the incidence and nature of acute and late toxicity of gemcitabine hydrochloride, cisplatin, and concurrent radiotherapy in patients with stage II or III transitional cell carcinoma of the bladder. (Phase I) Determine the efficacy of this regimen, in terms of local tumor control (absence of local progression), in these patients. (Phase II) Secondary Determine the maximum tolerated dose and the recommended phase II dose of gemcitabine hydrochloride when administered with cisplatin and radiotherapy in these patients. (Phase I) Assess the 5- and 10-year survival and the progression-free survival of patients treated with this regimen. (Phase II) Assess the quality of life of patients treated with this regimen. (Phase II) OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride followed by a phase II, multicenter study. Patients receive gemcitabine hydrochloride IV over 30 minutes twice weekly for 5 weeks and cisplatin IV continuously over 4 days on days 2-5 and 23-26 (weeks 1 and 4). Patients also undergo radiotherapy once daily 5 days a week for 5 weeks. Three weeks after completion of treatment, patients undergo cystoscopy and transurethral resection (TUR). Patients with residual tumor or disease progression undergo radical TUR. After surgery, patients who achieve a complete response receive gemcitabine hydrochloride IV twice weekly for 2 weeks and cisplatin IV continuously over 4 days in week 1. Patients also undergo radiotherapy once daily 5 days a week for 2 weeks. After completion of study treatment, patients are followed at 6-8 weeks and then 6 months thereafter.

Official Title
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Phase 1-2 Study of the Association of Gemzar ® - Cisplatin-concurrent Radiotherapy in Patients With Non-metastatic Tumors of the Bladder

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Procedure: biopsy
* Procedure: cystoscopy
* Procedure: therapeutic conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of muscle invasive transitional cell carcinoma of the bladder T2-4a, N0, M0 (stage II or III disease) No adenocarcinoma or squamous cell carcinoma PATIENT CHARACTERISTICS: WHO performance status (PS) 0-2 or Karnofsky PS 70-100% Life expectancy ≥ 6 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Creatinine clearance ≥ 60 mL/min Not pregnant or nursing Fertile patients must use effective contraception during and for at least 2 months after completion of study treatment No other prior malignancy, except previously treated nonmalignant skin cancer or carcinoma in situ of the cervix No prior serious digestive complications (e.g., ulcerative colitis or complicated diverticulosis) PRIOR CONCURRENT THERAPY: No prior radiotherapy or chemotherapy (except for intravesical instillations)

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: gemcitabine, cisplatine, radiotherapy<br> | Drug: cisplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Procedure: biopsy<br> <br> Procedure: cystoscopy<br> <br> Procedure: therapeutic 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 |
| --- | --- | --- |
| Incidence and nature of acute and late toxicity (Phase I) |  | From baseline to the end of treatment | 
| Local tumor control (Phase II) |  | From baseline to the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose and recommended phase II dose of gemcitabine hydrochloride when administered with cisplatin and radiotherapy (Phase I) |  | From baseline to the end of treatment | 
| 5- and 10-year survival (Phase II) |  | until 5 and 10 year after the end of treatment | 
| Progression-free survival (Phase II) |  | 6 to 8 weeks after to the end of treatment | 
| Quality of life (Phase II) |  | From baselin to the end of 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, transitional cell carcinoma of the bladder