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
Colección de datos
Enfermedades del colon+9
+ Enfermedades del Sistema Digestivo
+ Neoplasias del sistema digestivo
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de septiembre de 2003
Fecha en la que se inscribió al primer participante.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.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 37 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.De 18 a 75 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
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 Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.Objetivos del Estudio
Objetivos Primarios
Objetivos Secundarios
Centros del Estudio
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