Safety Study of Tarceva in Children With Refractory and Relapsed Malignant Brain Tumors and Newly Diagnosed Brain Stem Glioma

Study Overview
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Brief Summary
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The purpose of this study is to establish the recommended dose/Maximum Tolerated Dose (MTD) of Tarceva in children as single agent and in combination with radiation therapy

Detailed Description
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Prognosis in relapsing malignant brain tumors is poor. Those in brain stem gliomas is dismal; median survival of these children does not exceed 9 months. Radiation therapy may result in early and transient amelioration of symptoms, but have not contributed to increase or prolong survival. Moreover, chemotherapy has not increased this outcome to date.Prados et al. reported encouraging results from a phase I study of TarcevaTM/OSI-774 alone or with temozolomide (TMZ) in patients with malignant gliomas. Of 25 evaluated patients, 6 experienced PR: 4 GBM (glioblastoma multiforme) and 1 grade 3 astrocytoma treated with TarcevaTM alone, 1 GBM treated with TarcevaTM/TMZ; 2 had minor responses, and 3 stable diseases. These results in malignant glioma and the lack of efficacy in brain stem glioma with current treatment suggests the evaluation of this new therapeutic agent in children with relapsed brain tumors and upfront at diagnosis in brain stem glioma in combination with radiation therapy.

Official Title
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Phase I Studies of TarcevaTM (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

Conditions
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Malignant Brain Tumor, Brain Stem Glioma,

Intervention / Treatment
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* Drug: Tarceva (Erlotinib Hydrochloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed malignant brain tumor Disease must be considered refractory to first line or relapsing after conventional therapy and for which no effective conventional treatment exists.· Newly diagnosed, histologically proven brain stem glioma, except pilocytic astrocytomas. Age: 1 to ≤ 21 years of age at study entry Life expectancy: at least 8 weeks ECOG Performance status ≤ 1 or Lansky-Play Scale>= 70%, and including children with motor paresis due to disease Measurable or evaluable disease No other serious concomitant illness No organ toxicity > grade 2 NCI-CTC AE v3.0, except alopecia and neurological symptoms due to disease Exclusion Criteria: Patients with spontaneous intratumoral hemorrhage will not be included in the study, in exception of small post-biopsy hemorrhage due to biopsy procedure Pregnant and breast feeding woman Uncontrolled intercurrent illness or active infection Chemotherapy within 4 weeks prior to study medication (within 6 weeks, if the regimen contained a nitrosourea) Radiation therapy within 6 weeks prior to study medication Any clinical or non-clinical evidence of pulmonary dysfunction or pre-existing lung disease Severe cardiac pathology; history of myocardial infarction within the year prior to inclusion Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions Treatment with Coumarin (warfarin)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tarceva (Erlotinib Hydrochloride)|tablets of 25 mg, 100 mg and 150 mg 75 to 150 mg/m² Once daily|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the recommended dose / Maximum Tolerated Dose (MTD) the for phase II study for single agent and in combination with radiation therapy |  | End of recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define Dose Limiting Toxicities (DLTs) |  | 3 cycles-6 cycles | 
| To define the safety profile |  | End of treatment | 
| To characterize the pharmacokinetic behavior of TarcevaTM in children with brain tumors as a single agent and in combination with radiation therapy |  | Cycles 1,2,3,4,5,6 | 
| To evaluate efficacy |  | Cycles 2,4,6, end of treatment | 
| To evaluate expression and mutations of EGFR with efficacy |  | End of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tarceva, refractory and relapsed malignant brain tumors, newly diagnosed brain stem glioma