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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Transitional Cell Cancer of the Renal Pelvis and Ureter

Bladder Cancer

Treatments

Drug: ifosfamide

Drug: doxorubicin hydrochloride

Drug: paclitaxel

Drug: cisplatin

Biological: filgrastim

Drug: gemcitabine hydrochloride

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00003105

97-095

CDR0000065841 (Registry Identifier)

NCI-G97-1339

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

PRIOR CONCURRENT THERAPY:

Biologic therapy: