Erlotinib Alone or in Combination With Radiation Therapy in Treating Young Patients With Refractory or Relapsed Malignant Brain Tumors or Newly Diagnosed Brain Stem Glioma
Phase I Studies of TARCEVA™ (ERLOTINIB HYDROCHLORIDE, OSI-774) as Single Agent in Children With Refractory and Relapsed Malignant Brain Tumors and in Combination With Irradiation in Newly Diagnosed Brain Stem Glioma
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given alone or together with radiation therapy in treating young patients with refractory or relapsed malignant brain tumors or newly diagnosed brain stem glioma.
Visão geral do estudo
Status
Descrição detalhada
OBJECTIVES:
Primary
- Establish the maximum tolerated dose of single-agent erlotinib hydrochloride in pediatric patients with refractory or relapsed malignant brain tumors and in combination with radiotherapy in pediatric patients with newly diagnosed brain stem glioma.
Secondary
- Determine dose-limiting toxicities of these regimens.
- Define the safety profile of these regimens.
- Characterize the pharmacokinetic behavior of erlotinib hydrochloride in these patients.
- Evaluate the efficacy of these regimens.
- Correlate expression and mutations of epidermal growth factor receptor with treatment response.
OUTLINE: This is a multicenter, nonrandomized, open-label, dose-escalation study of erlotinib hydrochloride. Patients are assigned to 1 of 2 treatment groups according to disease.
- Group 1 (refractory or relapsed malignant brain tumors): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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 (DLT).
- Group 2 (newly diagnosed brain stem glioma): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Beginning on day 1, patients also undergo radiotherapy 5 days a week for 6 weeks .
Cohorts of 1-2 patients receive escalating doses of erlotinib hydrochloride until the MTD is determined. The MTD is defined as the dose resulting in 25% of patients experiencing DLT at 6 weeks.
Blood is collected for pharmacokinetic assessments and pharmacogenetic genotyping for analysis of enzyme polymorphisms. Tumor tissue may be assessed for epidermal growth factor receptor mutations.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Dublin, Irlanda, 12
- Our Lady's Hospital for Sick Children Crumlin
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England
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Birmingham, England, Reino Unido, B4 6NH
- Birmingham Children's Hospital
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Bristol, England, Reino Unido, BS2 8AE
- Institute of Child Health at University of Bristol
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Cambridge, England, Reino Unido, CB2 2QQ
- Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
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Leeds, England, Reino Unido, LS9 7TF
- Leeds Cancer Centre at St. James's University Hospital
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Leicester, England, Reino Unido, LE1 5WW
- Leicester Royal Infirmary
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Liverpool, England, Reino Unido, L12 2AP
- Royal Liverpool Children's Hospital, Alder Hey
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London, England, Reino Unido, WC1N 3JH
- Great Ormond Street Hospital for Children NHS Trust
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London, England, Reino Unido, W1T 3AA
- Middlesex Hospital
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Manchester, England, Reino Unido, M27 4HA
- Central Manchester and Manchester Children's University Hospitals NHS Trust
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Newcastle-Upon-Tyne, England, Reino Unido, NE1 4LP
- Sir James Spence Institute of Child Health
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Nottingham, England, Reino Unido, NG7 2UH
- Queen's Medical Centre
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Oxford, England, Reino Unido, 0X3 9DU
- Oxford Radcliffe Hospital
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Sheffield, England, Reino Unido, S10 2TH
- Children's Hospital - Sheffield
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Southampton, England, Reino Unido, SO16 6YD
- Southampton University Hospital NHS Trust
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Sutton, England, Reino Unido, SM2 5PT
- Royal Marsden NHS Foundation Trust - Surrey
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Northern Ireland
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Belfast, Northern Ireland, Reino Unido, BT12 6BE
- Royal Belfast Hospital for Sick Children
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Scotland
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Aberdeen, Scotland, Reino Unido, AB25 2ZG
- Royal Aberdeen Children's Hospital
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Edinburgh, Scotland, Reino Unido, EH9 1LF
- Royal Hospital for Sick Children
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Glasgow, Scotland, Reino Unido, G3 8SJ
- Royal Hospital for Sick Children
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Wales
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Cardiff, Wales, Reino Unido, CF14 4XW
- Childrens Hospital for Wales
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Histologically or cytologically confirmed malignant brain tumor
- Refractory to first-line therapy or relapsed after conventional therapy
- No effective conventional therapy exists
Histologically confirmed brain stem glioma
- Newly diagnosed disease
- No pilocytic glioma
- Measurable or evaluable disease
PATIENT CHARACTERISTICS:
WHO performance status 0-2 OR Lansky play scale 50-100%
- Patients with motor paresis due to disease are eligible
- Neurological deficits must be stable for ≥ 1 week
- Life expectancy ≥ 8 weeks
- Absolute neutrophil count > 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 8 g/dL
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 70 mL/min
- No other serious, uncontrolled illness
- No active infection
- No organ toxicity ≥ grade 2 except alopecia and neurological symptoms due to disease
Must be able to take oral medication
- Patients with newly diagnosed brain stem glioma with difficulty swallowing may be eligible
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of pulmonary dysfunction or pre-existing lung disease
- No myocardial infarction within the past year
- No severe cardiac pathology
No significant ophthalmologic abnormality including, but not limited to, any of the following:
- Severe dry eye syndrome
- Keratoconjunctivitis sicca
- Sjögren's syndrome
- Severe exposure keratitis
- Any other disorder likely to increase the risk of corneal epithelial lesions
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- More than 6 weeks since prior radiotherapy
- No concurrent warfarin
- No other concurrent anticancer or investigational agents
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Mascaramento: Nenhum (rótulo aberto)
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
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Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
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Medidas de resultados secundários
Medida de resultado |
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Segurança
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Eficácia
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Toxicidades limitantes de dose
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Pharmacokinetic behavior of erlotinib hydrocloride
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Correlation of expression and mutations of epidermal growth factor receptor with treatment response
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Darren Hargrave, MD, Royal Marsden NHS Foundation Trust
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
- glioma de tronco cerebral infantil não tratado
- ependimoma infratentorial da infância
- ependimoma supratentorial infantil
- Tumor neuroectodérmico primitivo supratentorial recorrente da infância
- astrocitoma cerebelar infantil recorrente
- astrocitoma cerebral infantil recorrente
- ependimoma infantil recorrente
- tumor cerebral infantil recorrente
- meduloblastoma infantil recorrente
- Via visual infantil recorrente e glioma hipotalâmico
- craniofaringioma infantil
- tumor de células germinativas do sistema nervoso central na infância
- tumor do plexo coróide na infância
- meningioma grau I da infância
- meningioma grau II da infância
- meningioma grau III da infância
- astrocitoma cerebral de baixo grau na infância
- pineoblastoma infantil recorrente
- Astrocitoma recorrente de células gigantes subependimárias da infância
Termos MeSH relevantes adicionais
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Neoplasias por Tipo Histológico
- Neoplasias
- Neoplasias por local
- Neoplasias Glandulares e Epiteliais
- Neoplasias Neuroepiteliais
- Tumores Neuroectodérmicos
- Neoplasias, Células Germinativas e Embrionárias
- Neoplasias, Tecido Nervoso
- Glioma
- Neoplasias Cerebrais
- Neoplasias do Sistema Nervoso
- Neoplasias do Sistema Nervoso Central
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Inibidores de proteína quinase
- Cloridrato De Erlotinibe
Outros números de identificação do estudo
- CDR0000481539
- CCLG-NAG-2005-09
- ITCC-003
- EU-20617
- CCLG-CPP-05-07
- ROCHE-MO18461
- EUDRACT-2004-005247-10
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