Clinical trial NCT00124657
Conditions: Brain and Central Nervous System Tumors
Keywords: adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult glioblastoma adult giant cell glioblastoma adult gliosarcoma adult mixed glioma childhood mixed glioma untreated childhood cerebellar astrocytoma childhood high-grade cerebral astrocytoma childhood low-grade cerebral astrocytoma childhood oligodendroglioma childhood spinal cord neoplasm
Sponsor: St. Jude Children's Research Hospital
Start date: 2005-03-01; Completion date: 2014-09-01
Enrollment: 62 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with radiation therapy and to see how well they work in treating young patients with newly diagnosed glioma.

Detailed description:
OBJECTIVES:

Primary

* Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered during and after radiotherapy in young patients with newly diagnosed high-grade glioma and unfavorable low-grade glioma.
* Determine the 1- and 2-year progression-free survival of patients treated with this regimen.

Secondary

* Determine the toxic effects of this regimen in these patients.
* Correlate genetic abnormalities in epidermal growth factor receptor (EGFR) and components of downstream pathways with treatment response in patients treated with this regimen.
* Determine the ability of erlotinib to inhibit EGFR signaling in patients with high-grade glioma who require second surgery.
* Determine the pharmacokinetics of erlotinib and its metabolites in these patients.
* Correlate plasma and cerebrospinal fluid levels of vascular endothelial growth factor and basic fibroblast growth factor with tumor response in patients treated with this regimen.
* Correlate irradiation dosimetry with patterns of failure, standard and investigational imaging, and toxicity in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of erlotinib followed by a phase II study.

* Phase I: Patients undergo radiotherapy once daily, 5 days week, for approximately 6½ weeks. Beginning on the first day of radiotherapy, patients receive oral erlotinib once daily for up to 2 years.

Cohorts of patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined.

* Phase II: Patients will receive erlotinib as in phase I at the MTD and undergo radiotherapy as in phase I.

PROJECTED ACCRUAL: A total of 75-80 patients (15-20 for the phase I portion and 60 for the phase II portion) will be accrued for this study.

Arms: arm 1: Patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and \<26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) are not eligible for this study. Patients with spinal cord tumors will be eligible for the Phase I and Phase II component of this study, but they will not be taken into consideration to estimate PFS in the Phase II component of this trial because of their notoriously worse prognosis. Patients receive erlotinib hydrochloride.
Interventions: intervention 1: Erlotinib hydrochloride
Intervention descriptions: intervention 1: This study has 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib will be given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study is 120mg/m2 per day (maximum dose of 200mg per day).

Protocol documents: