- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00602329
MRI in Predicting Response in Patients Receiving Combination Chemotherapy and Bevacizumab For Advanced or Metastatic Colorectal Cancer
A Phase II Study Assessing Tumor Blood Flow as Measured by Dynamic Contrast Enhanced MRI in Patients With Metastatic Colorectal Cancer Receiving FOLFOX Alone Versus Patients Randomized to Receive FOLFOX Plus Bevacizumab at 5mg/kg or 10mg/kg.
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. Diagnostic procedures, such as MRI, may help doctors predict a patient's response to treatment and help plan the best treatment.
PURPOSE: This randomized phase II trial is studying how well MRI works in predicting response to combination chemotherapy given together with bevacizumab in treating patients with advanced or metastatic colorectal cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- To determine the alteration of tumor blood flow using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced or metastatic colorectal cancer after 2 courses of combination chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin (FOLFOX) and bevacizumab at 5 mg/kg vs 10 mg/kg or FOLFOX alone.
Secondary
- To correlate tumor blood flow, as assessed by DCE-MRI, with time to progression in patients receiving bevacizumab at 5mg/kg vs 10mg/kg.
- To correlate vascular proliferation, as measured by DCE-MRI, with markers of endothelial cell proliferation (i.e., CD31, 34, 105; integrin αvß3; phospho-ERK; Ki67; PCNA; and smooth muscle actin).
- To obtain pilot data on whether assays that measure vascular endothelial cell mitogenic stimulation and mitogenic activity may predict response to therapy, time to progression, and overall survival of patients receiving bevacizumab at 5mg/kg vs 10mg/kg.
- To investigate the association of various markers of apoptosis in tumor cells (e.g., MIF, CREB, or HIF-1-alpha expression/polymorphism and others) and tumor vascularity, as assessed by DCE-MRI.
- To correlate markers of apoptosis in tumor cells with response to therapy, time to progression, and overall survival.
- To determine serum levels of VEGF prior to the initiation of chemotherapy and then prior to courses 2 and 3 of chemotherapy as potential markers of antiangiogenic activity.
OUTLINE: Patients who are eligible to receive bevacizumab are randomized to 1 of 2 treatment arms. Patients who are ineligible to receive bevacizumab receive FOLFOX alone.
- Arm I: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours (FOLFOX) beginning on day 1. Patients also receive bevacizumab at 5 mg/kg IV over 90 minutes on day 1. Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive FOLFOX as in arm I and bevacizumab at 10 mg/kg IV over 90 minutes on day 1. Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
- FOLFOX alone (control): Patients receive FOLFOX as in arm I. All patients undergo dynamic contrast-enhanced MRI at baseline and between courses 2 and 3 (between days 17 and 29) to assess tumor blood flow.
Tumor tissue specimens are obtained from prior colonoscopic biopsy or surgical resection in patients receiving bevacizumab. Tissue specimens are examined by immunohistochemistry to evaluate tumor markers of angiogenesis and apoptosis (e.g., CD31, 34, 105, phospho-ERK, PCNA, Ki67, SMA, and integrin αvß3). Blood specimens are obtained at baseline and prior to courses 2 and 3 (days 15 and 29) to evaluate plasma levels of VEGF.
After completion of study therapy, patients are followed every 2 months for 1 year and then every 3 months thereafter.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Estados Unidos, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
- Histologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum
Patients receiving bevacizumab must have tumor tissue available for immunohistochemical analysis
- Formalin-fixed, paraffin-embedded tissue from previous biopsy or surgical resection is sufficient
Measurable disease, defined by RECIST as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques (i.e., CT or MRI)
- CEA elevation alone is insufficient for study entry
- No known brain metastases
PATIENT CHARACTERISTICS:
Criteria for all patients
- ECOG performance status 0-1
- Life expectancy > 3 months
- Granulocytes ≥ 1,500/mL
- Platelet Count ≥ 100,000/mL
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- AST ≤ 5 times ULN
- Urine protein:creatinine ratio ≤ 1.0 at screening
- Patients with other prior malignancies are eligible, provided they have been treated with curative intent and have no evidence of recurrence
- Not pregnant or nursing
- Negative pregnancy test
No contraindications to MRI, including any of the following:
- Hypersensitivity to gadolinium
- Metallic device, including pacemaker, non-MRI compatible aneurysm clip, other non-MRI-compatible mechanical and/or electrical device, or metallic fragments
- Severe claustrophobia
Additional criteria for patients receiving bevacizumab:
- No significant traumatic injury within the past 28 days
- No serious nonhealing wounds, ulcers, or bone fractures
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No myocardial infarction, unstable angina, or cerebrovascular accident within the past 6 months
- No clinically significant peripheral vascular disease
- No New York Heart Association class II-IV congestive heart failure
- Patients with pre-existing hypertension should be on a stable antihypertensive regimen with blood pressure ≤ 150/100 mm Hg at study entry
PRIOR CONCURRENT THERAPY:
Criteria for all patients
- Prior adjuvant treatment including oxaliplatin allowed
- No prior bevacizumab
- At least 14 days since prior radiotherapy and recovered
- More than 6 months since prior chemotherapy
- No other concurrent investigational agents
Additional criteria for patients receiving bevacizumab:
- At least 28 days since prior major surgical procedure or open biopsy
- At least 7 days since prior minor surgical procedure (e.g., fine-needle aspirations or core biopsies)
- No anticipation of need for a major surgical procedure during study treatment
- Concurrent oral or parenteral anticoagulation therapy allowed provided dose is stable
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Diagnóstico
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Arm I
Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours (FOLFOX) beginning on day 1.
Patients also receive bevacizumab at 5 mg/kg IV over 90 minutes on day 1.
Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
|
Dado IV
Dado IV
Dado IV
Dado IV
|
Experimental: Arm II
Patients receive FOLFOX as in arm I and bevacizumab at 10 mg/kg IV over 90 minutes on day 1.
Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
|
Dado IV
Dado IV
Dado IV
Dado IV
|
Comparador activo: FOLFOX alone (control)
Patients receive FOLFOX as in arm I.
|
Dado IV
Dado IV
Dado IV
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Analysis of tumor blood flow, assessed by DCE-MRI as percentage change in Ktrans, after 2 courses of FOLFOX and bevacizumab or FOLFOX alone compared to baseline value
Periodo de tiempo: 2 cycles for all subjects
|
2 cycles for all subjects
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Analysis of tumor markers of angiogenesis and apoptosis, and the effect of treatment
Periodo de tiempo: 2 cycles for all subjects
|
2 cycles for all subjects
|
Correlation of tumor blood flow with time to progression
Periodo de tiempo: 2 cycles
|
2 cycles
|
Correlation of markers of apoptosis in tumor cells with response to therapy, time to progression, and overall survival
Periodo de tiempo: 2 cycles for all subjects
|
2 cycles for all subjects
|
Colaboradores e Investigadores
Colaboradores
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 (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
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
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes Protectores
- Agentes antineoplásicos inmunológicos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Micronutrientes
- Vitaminas
- Hormonas y agentes reguladores del calcio
- Antídotos
- Complejo de vitamina B
- Fluorouracilo
- Oxaliplatino
- Bevacizumab
- Leucovorina
- Calcio
- Levoleucovorina
Otros números de identificación del estudio
- CDR0000580810
- UPCC-09205
- GENENTECH-UPCC-09205
- UPCC-804021
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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. .
Ensayos clínicos sobre Cáncer colonrectal
-
Abramson Cancer Center of the University of PennsylvaniaTerminadoPaciente con cancerEstados Unidos
-
Peking Union Medical College HospitalTerminadoEncuesta | Estado nutricional | Paciente con cancerPorcelana
-
Ankara Medipol UniversityReclutamientoCuidados personales | Inmunoterapia | Manejo de síntomas | Paciente con cancerPavo
-
Northwestern UniversityGenzyme, a Sanofi CompanyRetiradoCANCER DE PROSTATAEstados Unidos
-
Fundacao ChampalimaudTerminado
-
University College London HospitalsTerminado
-
GenSpera, Inc.RetiradoCancer de prostata.Estados Unidos
-
University of Colorado, DenverColorado State UniversityRetiradoRealidad virtual | Diagnóstico por imagen | Educación del paciente | Paciente con cancerEstados Unidos
-
Dana-Farber Cancer InstituteTerminadoCancer de RIÑON | Cancer de prostata | Cáncer genitourinarioEstados Unidos
-
Rabin Medical CenterReclutamiento
Ensayos clínicos sobre bevacizumab
-
National Cancer Institute (NCI)Activo, no reclutandoCarcinoma de trompa de Falopio recidivante | Carcinoma de ovario recurrente | Carcinoma peritoneal primario recidivante | Cistadenocarcinoma de células claras de ovario | Adenocarcinoma endometrioide de ovario | Cistadenocarcinoma seroso de ovario | Adenocarcinoma de células claras endometriales | Adenocarcinoma seroso endometrial y otras condicionesEstados Unidos
-
National Cancer Institute (NCI)NRG OncologyTerminadoGlioblastoma | Gliosarcoma | Glioblastoma recurrente | Oligodendroglioma | Glioblastoma de células gigantes | Neoplasia cerebral recurrenteEstados Unidos, Canadá
-
M.D. Anderson Cancer CenterReclutamientoCarcinoma hepatocelular en estadio IB AJCC v8 | Carcinoma hepatocelular en estadio II AJCC v8 | Carcinoma hepatocelular resecable | Carcinoma hepatocelular en estadio I AJCC v8 | Carcinoma hepatocelular en estadio IA AJCC v8Estados Unidos
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)ReclutamientoCarcinoma de trompa de Falopio recidivante | Carcinoma de ovario recurrente | Carcinoma peritoneal primario recidivante | Adenocarcinoma endometrioide de ovario | Adenocarcinoma de células claras de ovario | Adenocarcinoma de las trompas de Falopio | Adenocarcinoma seroso de las trompas de Falopio y otras condicionesEstados Unidos
-
National Cancer Institute (NCI)Activo, no reclutandoMelanoma cutáneo en estadio IV AJCC v6 y v7 | Melanoma cutáneo en estadio IIIC AJCC v7 | Melanoma irresecableEstados Unidos
-
National Cancer Institute (NCI)TerminadoAdenocarcinoma de cuello uterino | Carcinoma adenoescamoso de cuello uterino | Carcinoma de células escamosas de cuello uterino, no especificado | Cáncer de cuello uterino en estadio IVA AJCC v6 y v7 | Carcinoma cervical recurrente | Cáncer de cuello uterino en estadio IV AJCC v6 y v7 | Cáncer...Estados Unidos
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; Celldex TherapeuticsReclutamientoCarcinoma de trompa de Falopio recidivante | Carcinoma de ovario recurrente | Carcinoma peritoneal primario recidivante | Adenocarcinoma seroso endometrial recidivante | Adenocarcinoma de células claras de ovario | Carcinoma de ovario resistente al platino recurrente | Carcinoma de ovario sensible... y otras condicionesEstados Unidos
-
National Cancer Institute (NCI)ReclutamientoSarcoma alveolar metastásico de partes blandas | Sarcoma alveolar de partes blandas irresecableEstados Unidos
-
National Cancer Institute (NCI)Activo, no reclutandoAdenocarcinoma endometrioide de ovario | Adenocarcinoma seroso peritoneal primario de alto grado | Adenocarcinoma endometrioide de las trompas de Falopio | Carcinoma de las trompas de Falopio resistente al platino | Carcinoma peritoneal primario resistente al platino | Adenocarcinoma seroso... y otras condicionesEstados Unidos, Canadá
-
City of Hope Medical CenterNational Cancer Institute (NCI)Activo, no reclutandoCarcinoma de células no pequeñas de pulmón metastásico | Cáncer de pulmón en estadio IVA AJCC v8 | Cáncer de pulmón en estadio IVB AJCC v8 | Cáncer de pulmón en estadio III AJCC v8 | Cáncer de pulmón en estadio IV AJCC v8 | Cáncer de pulmón en estadio IIIA AJCC v8 | Cáncer de pulmón en estadio... y otras condicionesEstados Unidos