A Phase I Study of Irinotecan in Combination With Fixed Dose Celecoxib in Patients With Advanced Colorectal Cancer
Collecte de données
Maladies du côlon+10
+ Diarrhée
+ Maladies du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 mars 2005
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: Primary * Determine the maximum tolerated dose of irinotecan when administered with celecoxib in patients with unresectable or metastatic colorectal cancer. Secondary * Determine the dose-limiting toxic effects and non-dose-limiting toxic effects of this regimen in these patients. * Determine the incidence and intensity of diarrhea and myelotoxicity in patients treated with this regimen. * Determine any responses in patients treated with this regimen. * Determine potential mechanisms for irinotecan-induced diarrhea and protective effects of celecoxib on diarrhea prevention in patients treated with this regimen. OUTLINE: This is a dose-escalation study of irinotecan. Patients are assigned to 1 of 2 treatment groups. * Group I: Patients receive a fixed dose of irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and oral celecoxib twice daily on days 10-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. * Group II: Patients receive irinotecan as in group I at escalating doses and oral celecoxib twice daily on days 0-42. Treatment continues as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 18-30 patients (9 for group I, 9-21 for group II) will be accrued for this study within 1-2 years.
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.2 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 colorectal cancer * Metastatic or unresectable disease * Failed first-line or second-line therapy OR recurred after receiving fluorouracil-based adjuvant chemotherapy * No known brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * More than 12 weeks Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * WBC ≥ 3,000/mm\^3 Hepatic * AST and ALT ≤ 2.5 times upper limit of normal * Bilirubin normal * No Gilbert's disease Renal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Gastrointestinal * Able to receive oral medications * No prior inflammatory bowel disease * No active ulcer disease or gastritis * No contraindications for sigmoidoscopy * No active colostomy Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No prior allergic reaction to compounds of similar chemical or biological composition to irinotecan, celecoxib, sulfonamides, or other study agents * No active or ongoing infection * No other concurrent uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy * See Disease Characteristics * No more than 2 prior different chemotherapy regimens, including adjuvant therapy * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * No prior irinotecan Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy and recovered * No prior radiotherapy of more than 3,000 cGy * No prior radiotherapy to extended marrow-generating fields * No prior abdomino-pelvic irradiation Surgery * No prior abdominoperineal resection Other * More than 2 weeks since prior cyclo-oxygenase-2 (COX-2) inhibitors * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No other anticancer therapy * No other concurrent COX-2 inhibitors * Low-dose aspirin allowed
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