Clinical trial NCT00080795: Neoadjuvant Ifosfamide, Doxorubicin, Gemcitabine, and Cisplatin in Treating Patients Who Are Undergoing Radical Cystectomy for Locally Advanced Carcinoma (Cancer) of the Urothelium
Official title: Phase II Trial of Neoadjuvant, Multi-Agent Chemotherapy For Locally Advanced Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: stage III bladder cancer
regional transitional cell cancer of the renal pelvis and ureter
anterior urethral cancer
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-08
Enrollment: 65
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as ifosfamide, doxorubicin, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them before surgery, may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well neoadjuvant combination chemotherapy works in treating patients undergoing radical cystectomy for locally advanced carcinoma of the urothelium.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate and 4-year disease-free survival of patients with locally advanced carcinoma of the urothelium undergoing radical cystectomy treated with neoadjuvant chemotherapy comprising ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide.

Secondary

* Compare perioperative morbidity and mortality of patients treated with this regimen vs historical standards.

OUTLINE: Patients receive neoadjuvant chemotherapy comprising ifosfamide IV over 3 hours on days 1-4, doxorubicin IV on day 3, gemcitabine IV over 30 minutes on days 2 and 4, and filgrastim (G-CSF) subcutaneously on days 7-12 or until blood counts recover. Treatment repeats every 3 weeks for a total of 3 courses. Patients then receive cisplatin IV, gemcitabine IV over 90 minutes, and ifosfamide IV over 30 minutes on day 1. Treatment repeats every 2 weeks for a total of 4-6 courses. Four to six weeks after the completion of all neoadjuvant chemotherapy, patients undergo cystectomy.

Patients are followed at 9, 12, 15, 18, 24, and 30 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 31-49 patients will be accrued for this study within 16-25 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed carcinoma of the urothelium, meeting 1 of the following criteria for locally advanced disease:

  * Clinical stage T3b disease, defined by presence of a mass on examination under anesthesia
  * Clinical stage T4a disease, defined by direct invasion of prostatic stroma, vagina, or rectum
  * Lymphovascular invasion on transurethral resection specimen
* Upper tract disease or micropapillary histology allowed
* No evidence of disease outside the pelvis

PATIENT CHARACTERISTICS:

Age

* Any age

Performance status

* 0-2

Life expectancy

* Not specified

Hematopoietic

* Bone marrow function adequate

Hepatic

* Liver function adequate

Renal

* Creatinine clearance ≥ 45 mL/min

Cardiovascular

* Ejection fraction ≥ 50%

Other

* Not pregnant
* No other malignancy likely to be life-threatening within the next 4 years

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics

Primary outcomes:
measure: Response rate
timeFrame: 6 weeks following treatment
measure: Disease-free survival at 4 years
timeFrame: 4 years
Secondary outcomes:
measure: Comparison of perioperative treatment morbidity and mortality with historical standards
timeFrame: Minimally reviewed following 6 weeks post treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Randall E. Millikan, MD, PhD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Colin P. Dinney, MD
role: STUDY_CHAIR
References: