Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Bladder Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003105

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients with metastatic or locally advanced bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter	Biological: filgrastim Drug: cisplatin Drug: doxorubicin hydrochloride Drug: gemcitabine hydrochloride Drug: ifosfamide Drug: paclitaxel	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the safety and toxicity of doxorubicin, gemcitabine, and filgrastim (G-CSF) followed by ifosfamide, paclitaxel, cisplatin, and G-CSF in patients with metastatic or locally advanced transitional cell carcinoma of the urothelium.
Determine the efficacy of this regimen in this patient population.

OUTLINE: This is a dose-escalation study of gemcitabine.

Patients receive doxorubicin IV over 30 minutes and gemcitabine IV on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 3-11. Treatment repeats every 2 weeks for 5 courses.

After completion of the fifth course, patients receive paclitaxel IV over 3 hours and cisplatin IV over 1 hour on day 1, ifosfamide IV over 1 hour on days 1-3, and G-CSF SC daily on days 6-17. Treatment repeats every 3-4 weeks for 4 courses.

Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the MTD.

PROJECTED ACCRUAL: A maximum of 20 patients will be accrued for phase I and a maximum of 10 patients will be accrued for phase II within 2-3 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Primary Purpose:

Treatment

Official Title:

Phase I/II Trial of Sequential Doxorubicin/Gemcitabine (AG) and Ifosfamide, Paclitaxel, and Cisplatin (ITP) Chemotherapy (AG-ITP) in Patients With Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium

Study Start Date :

Sep 1, 1997

Actual Primary Completion Date :

Aug 1, 2004

Actual Study Completion Date :

Aug 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed transitional cell carcinoma of the urothelium
Measurable disease, defined as unresectable or metastatic urothelial tract tumors OR
Evaluable disease, defined as T3b or T4a bladder tumors

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 70-100%

Life expectancy:

Not specified

Hematopoietic:

Granulocyte count greater than 1,500/mm^3
Platelet count greater than 150,000/mm^3

Hepatic:

Bilirubin less than 1.5 times normal
SGOT less than 2 times normal

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

No New York Heart Association class III or IV heart disease
No serious cardiac arrhythmias, including first, second, or third degree heart block
LVEF at least 50%

Other:

No uncontrolled infection
No other active malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
Fertile patients must use effective barrier contraception before, during, and for 6 months after study and are encouraged to continue for 2 years or longer after study