Safety Study of Tarceva in Children With Refractory and Relapsed Malignant Brain Tumors and Newly Diagnosed Brain Stem Glioma
Primary Purpose
Malignant Brain Tumor, Brain Stem Glioma,
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Tarceva (Erlotinib Hydrochloride)
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Brain Tumor focused on measuring Tarceva, refractory and relapsed malignant brain tumors, newly diagnosed brain stem glioma
Eligibility Criteria
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)
Sites / Locations
- Institut Gustave Roussy
Outcomes
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
Secondary Outcome Measures
To define Dose Limiting Toxicities (DLTs)
To define the safety profile
To characterize the pharmacokinetic behavior of TarcevaTM in children with brain tumors as a single agent and in combination with radiation therapy
To evaluate efficacy
To evaluate expression and mutations of EGFR with efficacy
Full Information
NCT ID
NCT00418327
First Posted
January 3, 2007
Last Updated
August 6, 2009
Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
1. Study Identification
Unique Protocol Identification Number
NCT00418327
Brief Title
Safety Study of Tarceva in Children With Refractory and Relapsed Malignant Brain Tumors and Newly Diagnosed Brain Stem Glioma
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 Type
Interventional
2. Study Status
Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
4. Oversight
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Brain Tumor, Brain Stem Glioma,
Keywords
Tarceva, refractory and relapsed malignant brain tumors, newly diagnosed brain stem glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Tarceva (Erlotinib Hydrochloride)
Intervention Description
tablets of 25 mg, 100 mg and 150 mg 75 to 150 mg/m² Once daily
Primary Outcome Measure Information:
Title
To establish the recommended dose / Maximum Tolerated Dose (MTD) the for phase II study for single agent and in combination with radiation therapy
Time Frame
End of recruitment
Secondary Outcome Measure Information:
Title
To define Dose Limiting Toxicities (DLTs)
Time Frame
3 cycles-6 cycles
Title
To define the safety profile
Time Frame
End of treatment
Title
To characterize the pharmacokinetic behavior of TarcevaTM in children with brain tumors as a single agent and in combination with radiation therapy
Time Frame
Cycles 1,2,3,4,5,6
Title
To evaluate efficacy
Time Frame
Cycles 2,4,6, end of treatment
Title
To evaluate expression and mutations of EGFR with efficacy
Time Frame
End of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vassal Gilles, Pr.
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
21653689
Citation
White-Koning M, Civade E, Geoerger B, Thomas F, Le Deley MC, Hennebelle I, Delord JP, Chatelut E, Vassal G. Population analysis of erlotinib in adults and children reveals pharmacokinetic characteristics as the main factor explaining tolerance particularities in children. Clin Cancer Res. 2011 Jul 15;17(14):4862-71. doi: 10.1158/1078-0432.CCR-10-3278. Epub 2011 Jun 8.
Results Reference
derived
Learn more about this trial
Safety Study of Tarceva in Children With Refractory and Relapsed Malignant Brain Tumors and Newly Diagnosed Brain Stem Glioma
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