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
- Conditions
- Brain and Central Nervous System Tumors
- Registration Number
- NCT00360854
- Lead Sponsor
- Children's Cancer and Leukaemia Group
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy
- Secondary Outcome Measures
Name Time Method Dose-limiting toxicities Safety Pharmacokinetic behavior of erlotinib hydrocloride Efficacy Correlation of expression and mutations of epidermal growth factor receptor with treatment response
Trial Locations
- Locations (20)
Our Lady's Hospital for Sick Children Crumlin
🇮🇪Dublin, Ireland
Leicester Royal Infirmary
🇬🇧Leicester, England, United Kingdom
Middlesex Hospital
🇬🇧London, England, United Kingdom
Royal Liverpool Children's Hospital, Alder Hey
🇬🇧Liverpool, England, United Kingdom
Central Manchester and Manchester Children's University Hospitals NHS Trust
🇬🇧Manchester, England, United Kingdom
Royal Marsden NHS Foundation Trust - Surrey
🇬🇧Sutton, England, United Kingdom
Royal Belfast Hospital for Sick Children
🇬🇧Belfast, Northern Ireland, United Kingdom
Children's Hospital - Sheffield
🇬🇧Sheffield, England, United Kingdom
Queen's Medical Centre
🇬🇧Nottingham, England, United Kingdom
Royal Aberdeen Children's Hospital
🇬🇧Aberdeen, Scotland, United Kingdom
Childrens Hospital for Wales
🇬🇧Cardiff, Wales, United Kingdom
Sir James Spence Institute of Child Health
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Great Ormond Street Hospital for Children NHS Trust
🇬🇧London, England, United Kingdom
Royal Hospital for Sick Children
🇬🇧Glasgow, Scotland, United Kingdom
Oxford Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham, England, United Kingdom
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, England, United Kingdom
Institute of Child Health at University of Bristol
🇬🇧Bristol, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Southampton University Hospital NHS Trust
🇬🇧Southampton, England, United Kingdom