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
18 Years
N/A
Both
Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Dean F. Bajorin, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000066319
NCT ID:
NCT00003342
Start Date:
December 1997
Completion Date:
Related Keywords:
- Bladder Cancer
- Transitional Cell Cancer of the Renal Pelvis and Ureter
- stage III bladder cancer
- stage IV bladder cancer
- transitional cell carcinoma of the bladder
- metastatic transitional cell cancer of the renal pelvis and ureter
- localized transitional cell cancer of the renal pelvis and ureter
- regional transitional cell cancer of the renal pelvis and ureter
- Urinary Bladder Neoplasms
- Carcinoma, Transitional Cell
- Kidney Neoplasms
- Ureteral Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
