- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00098761
VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors
Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors
RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.
Secondary
- Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
- Determine the efficacy of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).
Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
Patients are followed for 3 months.
PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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San Francisco, California, Estados Unidos, 94115
- UCSF Comprehensive Cancer Center
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010-2970
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60614
- Children's Memorial Hospital - Chicago
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38105
- St. Jude Children'S Research Hospital
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Texas
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Houston, Texas, Estados Unidos, 77030-2399
- Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Children's Hospital and Regional Medical Center - Seattle
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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* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)
- Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
- No bone marrow disease
PATIENT CHARACTERISTICS:
Age
- 21 and under
Performance status
- Karnofsky 50-100% (for patients > 16 years of age) OR
- Lansky 50-100% (for patients ≤ 16 years of age)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3*
- Platelet count ≥ 100,000/mm^3*
- Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT and AST ≤ 2.5 times ULN
- No overt hepatic disease
Renal
- BUN < 25 mg/dL
- Creatinine ≤ 1.5 times ULN for age OR
- Glomerular filtration rate > 70 mL/min
- No overt renal disease
Cardiovascular
- Shortening fraction ≥ 30% by echocardiogram OR
- Ejection fraction ≥ 50% by gated radionucleotide study
- No clinically significant cardiac arrhythmia by EKG
- No overt cardiac disease
Pulmonary
- DLCO ≥ 60% of predicted
- Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
- No overt pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
- No uncontrolled infection
- No known hypersensitivity to polyethylene glycol
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 6 months since prior allogeneic bone marrow or stem cell transplantation
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
- At least 3 weeks since prior myelosuppressive anticancer biologic therapy
- No concurrent routine colony-stimulating factors
Chemotherapy
- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy
- Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry
Radiotherapy
- At least 3 months since prior craniospinal irradiation ≥ 18 Gy
- At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites
Surgery
- Not specified
Other
- At least 7 days since prior nonmyelosuppressive anticancer therapy
- At least 7 days since prior investigational agents
- Concurrent enzyme-inducing anticonvulsant drugs allowed
- No other concurrent anticancer or experimental agents or therapies
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)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Estimate the maximum tolerated dose
Periodo de tiempo: First 6 weeks of therapy
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First 6 weeks of therapy
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Number of participants with dose limiting toxicities
Periodo de tiempo: First 6 weeks of therapy
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First 6 weeks of therapy
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Pharmacokinetics
Periodo de tiempo: Day 1 of therapy
|
Plasma samples for pharmacokinetic studies will be collected with the first dose of the study drug pre-infusion, and 5, 15, and 30 minutes, 1 hour, 2 hours, and 4 hours after the end of infusion.
VNP40101M plasma concentration-time data will be modeled and the individual pharmacokinetic pararmeters volume of the central compartment, elimination rate constant, and half-life will be estimated.
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Day 1 of therapy
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Tumor response to VNP40101M
Periodo de tiempo: Prior to course 3, 5, and 7 and end of therapy
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MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy
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Prior to course 3, 5, and 7 and end of therapy
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Sri Gururangan, MRCP (UK), Duke University
Publicaciones y enlaces útiles
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
Palabras clave
- astrocitoma cerebral infantil de alto grado
- ependimoma infratentorial infantil
- Tumor neuroectodérmico primitivo supratentorial infantil recurrente
- astrocitoma cerebeloso infantil recurrente
- astrocitoma cerebral infantil recurrente
- ependimoma infantil recurrente
- glioma de tronco encefálico infantil recurrente
- meduloblastoma infantil recurrente
- vía visual infantil recurrente y glioma hipotalámico
- craneofaringioma infantil
- tumor de células germinales del sistema nervioso central infantil
- tumor del plexo coroideo infantil
- meningioma infantil grado I
- meningioma infantil grado II
- meningioma infantil grado III
- astrocitoma cerebral infantil de bajo grado
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CDR0000396779
- PBTC-017
- VION-VNP40101M
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