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

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00418327

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Malignant Brain Tumor Brain Stem Glioma,	Drug: Tarceva (Erlotinib Hydrochloride)	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)