- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00083213
Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced Solid Tumors or Non-Hodgkin's Lymphoma
An Open Label, Sequential Cohort Dose-Escalation Safety, Tolerability and Pharmacokinetic Study of VEGF Trap Administered Intravenously in Patients With Advanced Solid Tumors or Lymphoma
RATIONALE: VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by stopping blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous VEGF Trap in treating patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.
Descripción general del estudio
Descripción detallada
OBJECTIVES:
Primary
- Determine the safety and tolerability of intravenous VEGF Trap in patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.
Secondary
- Determine the maximum tolerated intravenous dose of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the ability of this drug to bind circulating vascular endothelial growth factor in these patients.
- Determine, preliminarily, the ability of this drug to alter tumor blood flow and tumor vascular permeability in these patients.
- Determine whether antibodies to this drug develop in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive VEGF Trap IV over 1 hour on days 1 and 15 for a total of 2 doses.
Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose level.
In the absence of dose-limiting toxicity, patients with stable disease or partial or complete remission may continue to receive VEGF Trap on a separate extension protocol.
Patients are followed at weeks 1, 3, and 7 and then at 3 months.
PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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New York
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New York, New York, Estados Unidos, 10021
- Memorial Sloan - Kettering Cancer Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of one of the following:
- Non-Hodgkin's lymphoma
Primary or metastatic solid tumor located, by radiography, in at least one of the following sites:
- Liver
- Soft tissue
- Pelvis
- Other site that is suitable for delayed contrast-enhanced MRI (e.g., peripheral lung field)
Relapsed or refractory (including unresectable) disease
- Patients with solid tumors must have failed all curative chemotherapeutic regimens
- Patients with non-Hodgkin's lymphoma must be refractory to at least 2 standard chemotherapeutic regimens and rituximab
- Not amenable to available conventional therapies AND no standard therapy exists
- Measurable disease
- No prior or concurrent CNS metastases (brain or leptomeningeal)
- No primary intracranial tumor by MRI or CT scan
- No histologically confirmed squamous cell carcinoma of the lung
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- WBC ≥ 3,500/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100,000/mm^3
- No severe or uncontrolled hematologic condition
Hepatic
- Bilirubin ≤1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- PT and PTT normal
- INR normal
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal
- Creatinine ≤ ULN
- Urine protein/creatinine ratio ≤ 1
- No severe or uncontrolled renal condition
Cardiovascular
- No clinically significant acute electrocardiographic abnormalities
- LVEF normal by echocardiogram or MUGA within the past 12 months if there was prior exposure to anthracyclines
No untreated or uncontrolled hypertension
- No blood pressure > 150/100 mm Hg (despite treatment)
- No isolated systolic hypertension (i.e., systolic blood pressure > 180 mm Hg on at least 2 determinations [on separate days] within the past 3 months)
- No New York Heart Association class II - IV heart disease
- No active coronary artery disease requiring acute medical management
- No angina requiring acute medical management
- No congestive heart failure requiring acute medical management
- No ventricular arrhythmia requiring acute medical management
- No stroke or transient ischemic event within the past 6 months
No prior or concurrent peripheral vascular disease
- No angiographically or ultrasonographically documented arterial or venous occlusive event
- No symptomatic claudication
- No symptomatic orthostatic hypotension
- No other severe or uncontrolled cardiovascular condition
Pulmonary
- No severe or uncontrolled pulmonary condition
- No pulmonary embolism within the past 6 months
Immunologic
- HIV negative
- No severe or uncontrolled immunologic condition
- No active current infection requiring antibiotics
- No prior hypersensitivity reaction to any recombinant proteins, including VEGF Trap
Other
- No severe or uncontrolled gastrointestinal or musculoskeletal condition
- No psychiatric condition or adverse social circumstance that would preclude study participation
- No other condition that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for 3 months after study treatment
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior participation in a VEGF Trap, interleukin-1 Trap, or interleukin-4/13 Trap clinical trial
- At least 3 weeks since prior immunotherapy and recovered
- No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
Chemotherapy
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
Endocrine therapy
- No concurrent adrenal corticosteroids except low-dose replacement therapy
- No concurrent systemic hormonal contraceptive agents
Radiotherapy
- At least 3 weeks since prior radiotherapy and recovered
Surgery
- At least 3 weeks since prior major or laparoscopic surgery and recovered
- More than 6 months since prior surgical procedure for correction or prophylaxis of peripheral vascular insufficiency or cerebral ischemic events
Other
- More than 30 days since prior investigational drugs
- No concurrent anticoagulant or antiplatelet drugs (e.g., warfarin, heparin, or aspirin) other than low-dose (1 mg) warfarin for maintaining patency of venous access devices
- No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 (COX-2) inhibitors
- No other concurrent anticancer investigational agents
- No other concurrent anticancer therapy
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)
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: William P. Tew, MD, Memorial Sloan Kettering Cancer Center
Publicaciones y enlaces útiles
Publicaciones Generales
- Lockhart AC, Rothenberg ML, Dupont J, Cooper W, Chevalier P, Sternas L, Buzenet G, Koehler E, Sosman JA, Schwartz LH, Gultekin DH, Koutcher JA, Donnelly EF, Andal R, Dancy I, Spriggs DR, Tew WP. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol. 2010 Jan 10;28(2):207-14. doi: 10.1200/JCO.2009.22.9237. Epub 2009 Nov 30.
- Wang-Gillam A, Tew WP, Rothenberg ML, Dupont J, Cooper W, Sternas L, Buzenet G, Sosman JA, Spriggs DR, Lockhart AC. A phase I study of subcutaneously administered aflibercept (VEGF trap) in a new formulation in patients with advanced solid tumors. Invest New Drugs. 2012 Oct;30(5):1958-61. doi: 10.1007/s10637-011-9753-y. Epub 2011 Oct 15.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (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
Palabras clave
- Tumor testicular maligno de células germinativas en estadio III
- cáncer de vejiga recurrente
- cáncer de vejiga en estadio IV
- cáncer de próstata en estadio IV
- cáncer de próstata recurrente
- tumor sólido adulto no especificado, protocolo específico
- cáncer epitelial de ovario en estadio IV
- cáncer epitelial de ovario recurrente
- cáncer de trompa de Falopio
- linfoma folicular de grado 3 en estadio IV
- Linfoma difuso de células grandes en adultos en estadio IV
- Linfoma inmunoblástico de células grandes en adultos en estadio IV
- Linfoma de Burkitt en adultos en estadio IV
- linfoma folicular grado 3 recurrente
- Linfoma difuso de células grandes en adultos recidivante
- Linfoma inmunoblástico de células grandes en adultos recidivante
- Linfoma de Burkitt en adultos recidivante
- Linfoma difuso de células pequeñas hendidas en adultos recidivante
- Linfoma difuso de células mixtas en adultos recidivante
- linfoma folicular de grado 1 en estadio IV
- linfoma folicular de grado 2 en estadio IV
- Linfoma difuso de células pequeñas hendidas en adultos en estadio IV
- Linfoma difuso de células mixtas en adultos en estadio IV
- linfoma de células del manto en estadio IV
- cáncer primario de cavidad peritoneal
- cáncer de uretra distal
- cáncer de uretra proximal
- cáncer de uretra recurrente
- cáncer de uretra asociado con cáncer de vejiga invasivo
- linfoma folicular grado 1 recurrente
- linfoma folicular grado 2 recurrente
- linfoma de la zona marginal recurrente
- linfoma de linfocitos pequeños recurrente
- Linfoma de linfocitos pequeños en estadio IV
- linfoma de la zona marginal en estadio IV
- Linfoma extraganglionar de células B de la zona marginal de tejido linfoide asociado a mucosas
- linfoma de células B de la zona marginal ganglionar
- linfoma esplénico de la zona marginal
- cáncer primario de hígado en adultos avanzado
- cáncer de hígado primario recurrente en adultos
- carcinoma de endometrio en estadio IV
- carcinoma endometrial recurrente
- linfoma linfoblástico adulto recurrente
- linfoma de células del manto recurrente
- cáncer de cuello uterino en estadio IVA
- Linfoma linfoblástico en adultos en estadio IV
- Sarcoma de tejido blando en adultos en estadio IV
- Sarcoma de tejidos blandos en adultos recidivante
- sarcoma uterino estadio IV
- sarcoma uterino recurrente
- sarcoma de ovario
- cáncer de cuello uterino recurrente
- cáncer de cuello uterino en estadio IVB
- cáncer de estroma de ovario
- tumor de células germinales de ovario recurrente
- tumor de células germinales de ovario en estadio IV
- Tumor testicular maligno de células germinativas recurrente
- cáncer de vagina recurrente
- cáncer de vagina en estadio IVA
- cáncer de vagina en estadio IVB
- cáncer de vulva recurrente
- cáncer de pene recurrente
- cáncer de pene en estadio IV
- cáncer de vulva en estadio IVB
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Linfoma
- Efectos fisiológicos de las drogas
- Agentes antineoplásicos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Aflibercept
Otros números de identificación del estudio
- REGENERON-VGFT-ST-0202
- MSKCC-03137
- CDR0000360856 (Identificador de registro: PDQ (Physician Data Query))
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