A Phase II Study of 5-Fluorouracil Administered as a One Hour Infusion in Combination With Calcium Leucovorin and Interferon Alpha-2A in Advanced Colorectal Cancer
5-fluorouracil
Maladies du côlon+8
+ Maladies du système digestif
+ Néoplasmes du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 février 1995
Date à laquelle le premier participant a commencé l'étude.This protocol will evaluate the activity of 5-Fluorouracil (FUra) given as a 1 hour infusion in combination with leucovorin (LV) and interferon IFN alpha-2a in patients with advanced, measurable colorectal cancer. IFN alpha-2a will be given at 5 million U/m(2) SC days 1-6; LV, 200 mg/m(2), will be given as a short infusion over 30 minutes days 2-6, followed immediately by a 1 hour IV infusion of FUra days 2-6. The starting dose of FUra will be 425 mg/m(2)/d(1). Cycles will be repeated at three week intervals provided that the granulocyte count and platelet count have recovered to >e; 1200/microL and >e; 80,000/microL, respectively, and all non-hematologic toxicity has resolved. The dose of FUra will be adjusted according to individual tolerance. Preliminary experience with FUra given as a 1 hour infusion suggests that it is less toxic. The primary goal of this study is to determine if this less toxic regimen retains clinical antitumor activity. FUra plasma samples will be obtained the initial cycle at 50 and 55 minutes during the first 1 hour infusion of FUra to permit documentation of achieved plasma levels and to permit correlation between FUra pharmacokinetics and clinical toxicity and/or response. Pharmacokinetic sampling will be repeated if the dose of FUra is increased or decreased in subsequent cycles. Patients will be stratified according to whether or not they have received prior adjuvant chemotherapy. A two-stage design will be employed for patients with no prior chemotherapy: If less than or equal to 4 responses are seen among the initial 20 previously untreated patients, accrual will cease. If greater than or equal to 5 responses are seen in the initial 20 patients, however, accrual will be expanded to 40 patients. Fourteen patients who have received prior adjuvant chemotherapy (completing it at least 6 months prior to study entry) or have received prior FUra only as a radiation sensitizer will be entered. If no responses are seen, accrual to this cohort will cease. If greater than or equal to 1 response is seen, accrual may be expanded to 24 patients.
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.65 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.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: Unresectable primary colorectal adenocarcinoma that is metastatic or recurrent. Objectively measurable disease required. No cerebral metastases. PRIOR/CONCURRENT THERAPY: Biologic Therapy: No history of intolerance to interferon alfa (IFN-A). At least 4 weeks since immunotherapy and recovered. Chemotherapy: No prior chemotherapy for metastatic or recurrent disease. At least 6 months since adjuvant chemotherapy with fluorouracil (5-FU) in combination with levamisole, leucovorin (CF), or IFN-A Interval waived for 5-FU (with or without CF) as a radiosensitizer only . No dose-limiting toxicity with prior 5-FU. Endocrine Therapy: Not specified Radiotherapy: At least 2 weeks since palliative radiotherapy and recovered. Prior definitive pelvic or whole or upper abdominal radiotherapy allowed in the absence of current radiation enteritis. Surgery: Prior surgery allowed with adequate healing/recovery Patient Characteristics: Age: 18 and over. Performance status: ECOG 0 or 1. Hematopoietic: AGC at least 2,000. Platelets at least 100,000. Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No MI within the past year. No active ischemic heart disease. No NYHA class III/IV status. No symptomatic arrhythmia. OTHER: No requirement for pharmacologic steroid doses for inflammatory or autoimmune disorders. Physiologic replacement doses of steroids allowed. No concurrent cimetidine or oxypurinol. No HIV antibody. No history of seizure disorder. No active infection or other serious concurrent medical illness that would preclude treatment. No second malignancy within 3 years except curatively treated: In situ carcinoma of cervix, Basal cell carcinoma of the skin. No pregnant or nursing women. Effective contraception required of fertile patients.
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 1 site
National Cancer Institute (NCI)
Bethesda, United StatesOuvrir National Cancer Institute (NCI) dans Google Maps