Erlotinib Alone or in Combination With Radiation Therapy in Treating Young Patients With Refractory or Relapsed Malignant Brain Tumors or Newly Diagnosed Brain Stem Glioma
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given alone or together with radiation therapy in treating young patients with refractory or relapsed malignant brain tumors or newly diagnosed brain stem glioma.
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Genetic: mutation analysis
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Other: pharmacological study
Radiation: radiation therapy
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Studies of TARCEVA™ (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|
- Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
- Dose-limiting toxicities
- Pharmacokinetic behavior of erlotinib hydrocloride
- Correlation of expression and mutations of epidermal growth factor receptor with treatment response
|Study Start Date:||May 2005|
- Establish the maximum tolerated dose of single-agent erlotinib hydrochloride in pediatric patients with refractory or relapsed malignant brain tumors and in combination with radiotherapy in pediatric patients with newly diagnosed brain stem glioma.
- Determine dose-limiting toxicities of these regimens.
- Define the safety profile of these regimens.
- Characterize the pharmacokinetic behavior of erlotinib hydrochloride in these patients.
- Evaluate the efficacy of these regimens.
- Correlate expression and mutations of epidermal growth factor receptor with treatment response.
OUTLINE: This is a multicenter, nonrandomized, open-label, dose-escalation study of erlotinib hydrochloride. Patients are assigned to 1 of 2 treatment groups according to disease.
- Group 1 (refractory or relapsed malignant brain tumors): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).
- Group 2 (newly diagnosed brain stem glioma): Patients receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Beginning on day 1, patients also undergo radiotherapy 5 days a week for 6 weeks .
Cohorts of 1-2 patients receive escalating doses of erlotinib hydrochloride until the MTD is determined. The MTD is defined as the dose resulting in 25% of patients experiencing DLT at 6 weeks.
Blood is collected for pharmacokinetic assessments and pharmacogenetic genotyping for analysis of enzyme polymorphisms. Tumor tissue may be assessed for epidermal growth factor receptor mutations.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00360854
|Our Lady's Hospital for Sick Children Crumlin|
|Dublin, Ireland, 12|
|Birmingham Children's Hospital|
|Birmingham, England, United Kingdom, B4 6NH|
|Institute of Child Health at University of Bristol|
|Bristol, England, United Kingdom, BS2 8AE|
|Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Leicester Royal Infirmary|
|Leicester, England, United Kingdom, LE1 5WW|
|Royal Liverpool Children's Hospital, Alder Hey|
|Liverpool, England, United Kingdom, L12 2AP|
|London, England, United Kingdom, W1T 3AA|
|Great Ormond Street Hospital for Children NHS Trust|
|London, England, United Kingdom, WC1N 3JH|
|Central Manchester and Manchester Children's University Hospitals NHS Trust|
|Manchester, England, United Kingdom, M27 4HA|
|Sir James Spence Institute of Child Health|
|Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP|
|Queen's Medical Centre|
|Nottingham, England, United Kingdom, NG7 2UH|
|Oxford Radcliffe Hospital|
|Oxford, England, United Kingdom, 0X3 9DU|
|Children's Hospital - Sheffield|
|Sheffield, England, United Kingdom, S10 2TH|
|Southampton University Hospital NHS Trust|
|Southampton, England, United Kingdom, SO16 6YD|
|Royal Marsden NHS Foundation Trust - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Royal Belfast Hospital for Sick Children|
|Belfast, Northern Ireland, United Kingdom, BT12 6BE|
|Royal Aberdeen Children's Hospital|
|Aberdeen, Scotland, United Kingdom, AB25 2ZG|
|Royal Hospital for Sick Children|
|Edinburgh, Scotland, United Kingdom, EH9 1LF|
|Royal Hospital for Sick Children|
|Glasgow, Scotland, United Kingdom, G3 8SJ|
|Childrens Hospital for Wales|
|Cardiff, Wales, United Kingdom, CF14 4XW|
|OverallOfficial:||Darren Hargrave, MD||Royal Marsden NHS Foundation Trust|