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

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

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.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; Drug/Agent Toxicity by Tissue/Organ
• Intervention / Treatment: Drug: amifostine trihydrate; Procedure: adjuvant therapy; Drug: cisplatin; Drug: gemcitabine hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of Cisplatin, Gemcitabine, and Amifostine; 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; Procedure: adjuvant therapy; Drug: cisplatin; Drug: gemcitabine hydrochloride

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 2000
• Primary Completion (Actual): November 1, 2004
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: August 3, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stage III bladder cancer; stage IV bladder cancer; drug/agent toxicity by tissue/organ; stage II bladder cancer
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Radiation-Protective Agents; Gemcitabine; Amifostine
• Other Study ID Numbers: 9193; UCCRC-9193; UCCRC-CTRC-9806; NCI-G00-1831