A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer
Collecte de données
Maladies du côlon+9
+ Maladies du système digestif
+ Néoplasmes du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 septembre 2003
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: Primary * Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when combined with radiotherapy in patients with locally advanced adenocarcinoma of the rectum. (Phase I closed to accrual as of 06/2005.) * Determine the rate of complete pathological response in patients treated with this regimen. Secondary * Determine the overall survival of patients treated with this regimen. * Determine the rate of local and overall failure in patients treated with this regimen. * Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in patients treated with this regimen. * Determine the rate of pathologic down-staging in patients treated with this regimen. * Determine the safety and toxicity of this regimen in these patients. * Determine the rate of sphincter-saving rectal surgery in patients treated with this regimen who had been deemed candidates for abdominoperineal resection at diagnosis. OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005), dose-escalation study of oxaliplatin and capecitabine followed by a phase II study. * Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks and receive oral capecitabine twice daily on days radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and capecitabine 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. * Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in phase I at the MTD. All patients undergo curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy. Patients are followed every 3 months for 3 years and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I \[phase I closed to accrual as of 06/2005\] and 25 for phase II) will be accrued for this study within 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.37 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.De 18 à 75 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 adenocarcinoma of the rectum * Tumor involving the distal 12 cm of the rectum (above the anal verge) * Clinically staged by endoscopic ultrasound with one of the following criteria: * T3-T4 disease * Evidence of lymph node involvement, defined by the presence of ≥ 1 enlarged peri-rectal lymph node (≥ 1 cm in size) * No known distant metastases PATIENT CHARACTERISTICS: Age * 18 to 75 Performance status * ECOG 0-1 OR * Karnofsky 70-100% Life expectancy * More than 1 year Hematopoietic * WBC ≥ 3,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal Renal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Other * Able to receive oral medication * No other malignancy within the past 5 years except nonmelanoma skin cancer * No prior or concurrent significant neuropathy * No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs * No ongoing or active infection * No other concurrent uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-method contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent granulocyte-stimulating factors Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior pelvic radiotherapy Surgery * Not specified Other * No other concurrent investigational agents * No other concurrent anticancer agents or therapies
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Objectifs de l'étude
Objectifs principaux
Objectifs secondaires
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