Combination Chemotherapy in Treating Patients With Advanced Bladder or Kidney Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003342

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

115

Duration (Months)

Patients Per Site

0.1

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: This phase I trial is studying the side effects of giving gemcitabine, doxorubicin, and paclitaxel together with carboplatin in treating patients with advanced bladder or kidney cancer and impaired kidney function.

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

Detailed Description

OBJECTIVES:

Determine the safety and toxicity of dose-dense carboplatin plus paclitaxel on a weekly schedule given in sequence after gemcitabine and doxorubicin in patients with renal impairment and metastatic or locally advanced transitional cell carcinoma of the urothelium.
Observe the outcome of this sequential systemic chemotherapy in these patients, or following surgical resection as adjuvant therapy in patients in whom poor renal function precludes the use of cisplatin-based chemotherapy.

OUTLINE: This is a dose escalation study of carboplatin.

Patients receive gemcitabine IV over 10 minutes and doxorubicin IV over 15 minutes for 5 doses on weeks 1, 3, 5, 7, and 9. Filgrastim (G-CSF) is given subcutaneously on days 3 through 10 of each 2-week course. On week 11, patients receive paclitaxel and carboplatin IV over 1 hour weekly for 12 weeks.

Each cohort of 3 patients is entered on sequentially increasing doses of carboplatin. If any patient experiences dose limiting toxicity (DLT), then 6 patients are entered at that dose level. If 3 patients experience DLT at any dose level, the maximum tolerated dose has been surpassed and a total of 6 patients are treated at the previous level.

Patients are evaluated at week 16 and at end of study.

PROJECTED ACCRUAL: There will be 18-30 patients accrued into this study over 9-15 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Primary Purpose:

Treatment

Official Title:

Phase I Trial of Dose-Dense Gemcitabine, Doxorubicin, Then Paclitaxel Plus Carboplatin In Patients With Transitional Cell Carcinoma of the Urothelium and Impaired Renal Function

Study Start Date :

Dec 1, 1997

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2007

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 advanced transitional cell urothelial cancer
Clinical Stage IV: T any, N1-3, M0; T any, N any, M1; or cT4, Nx, M0 (bladder tumors)
Pathological Stage III or IV bladder cancer: T any, N1-3, M0; T3b, N0, M0; T4, N0, M0; and T4, Nx, M0
Pathological Stage III or IV urothelial cancer of the renal pelvis or ureter: T any, N1-3, M0; T3, N0, M0; T4, N0, M0; and surgery has been performed within 10 weeks of initiation of therapy
Impaired renal function (See Renal function tests)

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100% OR
ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

Granulocyte count at least 1,500/mm^3
Platelet count at least 150,000/mm^3

Hepatic:

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

Renal:

Creatinine greater than 1.5 mg/dL but no greater than 2.5 mg/dL OR
Creatinine clearance 30-59 mL/min

Cardiovascular:

Normal cardiac function by history, physical examination, and chest radiograph OR
If prior cardiac disease, left ventricular ejection fraction must be at least 50% by radionuclide ventriculogram or echocardiogram
No serious cardiac arrhythmias; including first, second, and third degree heart block
No New York Heart Association class III or IV heart disease

Other:

No uncontrolled infection
No other active cancer, except nonmelanomatous skin cancer and in situ carcinoma of the cervix curatively treated
Not pregnant
Effective barrier contraception required for all fertile patients during and for 6 months after therapy (encouraged to continue for 2 years or longer)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior systemic chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy to the bladder
At least 4 weeks since any other prior radiotherapy

Surgery:

See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
2	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021