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
filgrastim
+ carboplatin
+ doxorubicin hydrochloride
Maladies génito-urinaires+8
+ Maladies de la vessie urinaire
+ Maladies urogénitales féminines et complications de la grossesse
Étude thérapeutique
Résumé
Date de début de l'étude : 1 décembre 1997
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.30 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 2 sites
Memorial Sloan-Kettering Cancer Center
New York, United StatesOuvrir Memorial Sloan-Kettering Cancer Center dans Google MapsNew York Weill Cornell Cancer Center at Cornell University
New York, United States