Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Erlotinib hydrochloride
Intervention type(s): Drug
Intervention description(s): 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).
Other intervention name(s): Tarceva; OSI-774; NSC#718781
Intervention MeSH terms: Erlotinib Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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