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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

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