- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02573220
Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer
A UGT1A1 Genotype-Guided Dosing Study of Irinotecan Administered in Combination With 5-Fluorouracil/Leucovorin (FOLFIRI) and Cetuximab as First-Line Therapy in RAS Wild-Type Metastatic Colorectal Cancer Patients
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
PRIMARY OBJECTIVES:
I. To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the phase II recommended dosage of irinotecan (irinotecan hydrochloride) administered in the FOLFIRI regimen plus cetuximab in metastatic colorectal cancer (mCRC) patients with *1/*1 and *1/*28 uridine diphosphate glucuronosyltransferase (UGT1A1) genotype treated as first line chemotherapy.
SECONDARY OBJECTIVE:
To estimate the response rate, progression-free survival (PFS) and metastasectomy (with curative intent) rate in the overall patient population (both genotype cohorts).
OTHER OBJECTIVES:
I. To evaluate the variability of irinotecan pharmacokinetics, in combination with cetuximab, in patients with *1/*1 and *1/*28 genotype and the effect of the pharmacokinetic profile on toxicity and response rate.
II. To evaluate the pharmacokinetic profile of irinotecan and its major metabolites in the absence and the presence of cetuximab administration, in order to define the effect of the chimeric monoclonal antibody on irinotecan pharmacokinetics.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride in patients with UGT1A1.
Patients receive irinotecan hydrochloride intravenously (IV) over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tipo de estudio
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Aviano, Italia, 33081
- Centro Di Riferimento Oncologico
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of mCRC
- RAS wild-type status (by a Clinical Laboratory Improvement Amendments [CLIA] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog [KRAS], Harvey rat sarcoma viral oncogene homolog [HRAS], and neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS])
- No prior chemotherapy for metastatic disease
- Able to understand and provide written informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy > 3 months
- Measurable or evaluable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria, i.e. lesions that can be accurately measured in at least one dimension with the longest diameter >= 20 mm using conventional techniques or >= 10 mm using spiral computed tomography (CT) scan
- Absolute neutrophil count (ANC) > l500/ul
- Hemoglobin > 9g/dL
- Platelets > 100,000/ul
- Total bilirubin =< 1.5 times upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
- Alkaline phosphatase < 2.5 times the upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
- Creatinine < 1.5 mg/dL
- Patients genotyped for UGT1A1*28 polymorphism with *1/*1 or *1/*28 genotype
- Men and women of childbearing potential must agree to use adequate contraception (double barrier birth control) for the duration of study therapy
- Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential
Exclusion Criteria:
- Patients with both variant alleles (*28/*28)
- Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g, *6)
- Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis
- Patients with specific contraindications to the use of anti-EGFR therapy such as pulmonary fibrosis, interstitial pneumonia history
- Unresolved diarrhea and bowel obstruction
- Active bleeding
- Documented cerebral metastasis
- Serious active infectious disease
- Pregnancy
- Radiotherapy or major surgery within 4 weeks
- Psychiatric illness or social situations that would limit compliance with study requirements
- Presence of previous or concomitant neoplasm with exclusion of in situ cervical cancer
- Patients taking substrates, inhibitors and inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Treatment (FOLFIRI and cetuximab)
Patients receive irinotecan hydrochloride IV over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15.
Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Dado IV
Otros nombres:
Dado IV
Otros nombres:
Dado IV
Otros nombres:
Dado IV
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Maximum Tolerated Dose (MTD)
Periodo de tiempo: 28 days
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The MTD recommended for phase II studies will be defined as the dose level immediately below the one at which 1 out of 3 patients or 1 out of 6 patients experienced DLT.
Therefore at the MTD, 1/3 out of at least 10 patients experienced DLT.
No intra-patient dose escalation is allowed.
There will be two genotype cohorts of patients: one for each genotype.
The cumulative hematological and non-hematological toxicities as well as the number of dose reductions and a delay in starting the next cycle of treatment will be used as secondary indicators to differentiate the two genotype cohorts of patients.
Patients can continue receiving the same dose of irinotecan in the absence of major toxicity if before retreatment they fully recover from any non-hematological toxicity, absolute neutrophil count is 1500 microliters and platelet count is 100,000 microliters.
Chemotherapy is discontinued on evidence of disease progression by RECIST version 1.1.
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28 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Response rate
Periodo de tiempo: Every 2 cycles (every 8 weeks), from the beginning of the study until disease progression or death, which ever comes first (up to on average 60 months)
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Response rate is the number of patients with a partial response (by RECIST version 1.1) divided by the total number of patients.
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Every 2 cycles (every 8 weeks), from the beginning of the study until disease progression or death, which ever comes first (up to on average 60 months)
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Progression-free survival (PFS)
Periodo de tiempo: From beginning of the study until disease progression or death, which every comes first (up to on average 60 months)
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PFS is the time (in days) between study enrollment and disease progression (by RECIST version 1.1) or death, whichever comes first.
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From beginning of the study until disease progression or death, which every comes first (up to on average 60 months)
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metastectomy (with curative intent) rate
Periodo de tiempo: Within 1 year of starting therapy
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Metastatectomy rate is the number of patients who undergo a surgical resection with curative intent divided by the total number of patients
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Within 1 year of starting therapy
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Manish Sharma, University of Chicago Comprehensive Cancer Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Neoplasias
- Neoplasias por sitio
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Colon
- Enfermedades intestinales
- Neoplasias Intestinales
- Enfermedades Rectales
- Neoplasias colorrectales
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes Protectores
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa
- Agentes antineoplásicos inmunológicos
- Micronutrientes
- Vitaminas
- Hormonas y agentes reguladores del calcio
- Inhibidores de la topoisomerasa I
- Antídotos
- Complejo de vitamina B
- Fluorouracilo
- Leucovorina
- Irinotecán
- Calcio
- Levoleucovorina
- Cetuximab
- Camptotecina
Otros números de identificación del estudio
- IRB15-0081 (Otro identificador: University of Chicago Comprehensive Cancer Center)
- P30CA014599 (Subvención/contrato del NIH de EE. UU.)
- NCI-2015-01432 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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