A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
irinotecan hydrochloride
+ oxaliplatin
+ capecitabine
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de noviembre de 2003
Fecha en la que se inscribió al primer participante.OBJECTIVES: I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7). II. To identify any activity of this treatment combination in patients with metastatic cancer. III. To examine the differences in the toxicity profile, especially pertaining to hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes. IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its metabolites. OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1 genotype (6/6 vs 6/7 \[closed to accrual as of 8/24/06\] vs 7/7). Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, 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. Once the MTD is determined, an additional 6-10 patients (for a total of 12 patients) receive treatment at that dose. After completion of study treatment, patients are followed up at 3 months. PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II \[closed to accrual as of 8/24/06\], and 24-34 for stratum III) will be accrued for this study within approximately 4.4 years.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 84 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.A partir de 18 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.Criterios
Inclusion Criteria: * Histologically confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy * Unresectable disease * Willing to provide biologic specimens to determine UGT1A1 genotype * No CNS metastases * Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks * Performance status - ECOG 0-2 * At least 12 weeks * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 9.0 g/dL * Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 \[closed to accrual as of 8/24/06\] or 7/7 UGT1A1 genotype) * AST no greater than 3 times ULN (5 times ULN if there is liver involvement) * Creatinine no greater than 1.5 times ULN * No New York Heart Association class III or IV heart disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy * No uncontrolled infection * No seizure disorder * No peripheral neuropathy grade 2 or greater * More than 4 weeks since prior biologic therapy * More than 4 weeks since prior immunotherapy * No concurrent immunotherapy * No concurrent prophylactic colony-stimulating factor therapy * More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered * No other concurrent chemotherapy * See Disease Characteristics * More than 4 weeks since prior radiotherapy * No prior radiotherapy to more than 25% of the bone marrow * No concurrent radiotherapy * See Disease Characteristics * No other concurrent investigational therapy * No concurrent sorivudine, brivudine, lamivudine, or stavudine * No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent
Plan de Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.Un solo grupo de intervención está designado en este estudio
0% de probabilidad de ser asignado al grupo placebo
Grupos de Tratamiento
Grupo I
ExperimentalObjetivos del Estudio
Objetivos Primarios
Objetivos Secundarios
Centros del Estudio
Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.Este estudio tiene una ubicación