Clinical trial NCT00003342: Combination Chemotherapy in Treating Patients With Advanced Bladder or Kidney Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Dean F. Bajorin, MD
role: STUDY_CHAIR
References: