Gemcitabine, Cisplatin, and Amifostine Following Surgery in Treating Patients With Locally Advanced Bladder Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine, cisplatin, and amifostine following surgery in treating patients who have locally advanced bladder cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the toxicity of adjuvant gemcitabine and cisplatin with amifostine cytoprotection in patients with completely resected locally advanced bladder cancer. Compare recurrence rate in these patients when treated with this regimen to historical control patients who had a cystectomy performed by the same surgeon. OUTLINE: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15, and cisplatin IV over 60 minutes and amifostine IV over 15 minutes on day 1. Treatment continues every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months. PROJECTED ACCRUAL: A total of 19-42 patients will be accrued for this study.

Official Title
-----------------
Phase II Trial of Adjuvant Gemcitabine Plus Cisplatin With Amifostine Cytoprotection in Patients With Locally Advanced Bladder Cancer

Conditions
-----------------
Bladder Cancer, Drug/Agent Toxicity by Tissue/Organ

Intervention / Treatment
-----------------
* Drug: amifostine trihydrate
* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Procedure: adjuvant therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Completely resected locally advanced bladder cancer T2-4, N0-2 Post radical cystectomy with no gross residual disease No evidence of metastases by CT of chest, abdomen, and pelvis PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST and ALT no greater than 3 times ULN Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception during and for 3 months after study participation No active infection No serious concurrent systemic disorders that would preclude study participation No metastatic cancer in past 5 years PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except contraceptives and replacement steroids Radiotherapy: No concurrent radiotherapy Surgery: See Disease Characteristics At least 4 but no more than 8 weeks since radical cystectomy Other: No other concurrent experimental medications

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of Cisplatin, Gemcitabine, and Amifostine<br>Subjects receive the study drug combination in 29-day cycles. Gemcitabine (1000 mg/m2) is given by IV infusion on Days 1, 8, and 15 of each cycle. Cisplatin (70 mg/m2) is given by IV infusion on Day 1 of each cycle. Immediately prior to each cisplatin infusion amifostine (910 mg/m2) will be given by IV infusion. | Drug: amifostine trihydrate<br> <br> Drug: cisplatin<br> <br> Drug: gemcitabine hydrochloride<br> <br> Procedure: adjuvant therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects of cisplatin/gemcitabine in combination with amifostine |  | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II bladder cancer, stage III bladder cancer, stage IV bladder cancer, drug/agent toxicity by tissue/organ