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

Malignant Brain Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00418327
• Other study ID #: CSET 1120
• Status: Completed
• Phase: Phase 1
• First received: January 3, 2007
• Last updated: August 6, 2009
• Start date: June 2005

Study information

• Verified date: August 2009
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 48
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Stem Glioma,
• Glioma
• Malignant Brain Tumor

Intervention

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

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To define Dose Limiting Toxicities (DLTs)		3 cycles-6 cycles	Yes
Secondary	To define the safety profile		End of treatment	Yes
Secondary	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	Yes
Secondary	To evaluate efficacy		Cycles 2,4,6, end of treatment	No
Secondary	To evaluate expression and mutations of EGFR with efficacy		End of treatment	No