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
The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was Active, not recruiting
Recruitment status was Active, not recruiting
Sponsor:
Children's Cancer and Leukaemia Group
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00360854
First received: August 3, 2006
Last updated: February 6, 2009
Last verified: June 2007
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
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 |
Phase 1 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Dose-limiting toxicities [ Designated as safety issue: Yes ]
- Safety [ Designated as safety issue: Yes ]
- Pharmacokinetic behavior of erlotinib hydrocloride [ Designated as safety issue: No ]
- Efficacy [ Designated as safety issue: No ]
- Correlation of expression and mutations of epidermal growth factor receptor with treatment response [ Designated as safety issue: No ]
| Estimated Enrollment: | 48 |
| Study Start Date: | May 2005 |
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.
Eligibility| Ages Eligible for Study: | 1 Year to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Histologically or cytologically confirmed malignant brain tumor
- Refractory to first-line therapy or relapsed after conventional therapy
- No effective conventional therapy exists
Histologically confirmed brain stem glioma
- Newly diagnosed disease
- No pilocytic glioma
- Measurable or evaluable disease
PATIENT CHARACTERISTICS:
WHO performance status 0-2 OR Lansky play scale 50-100%
- Patients with motor paresis due to disease are eligible
- Neurological deficits must be stable for ≥ 1 week
- Life expectancy ≥ 8 weeks
- Absolute neutrophil count > 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 8 g/dL
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 70 mL/min
- No other serious, uncontrolled illness
- No active infection
- No organ toxicity ≥ grade 2 except alopecia and neurological symptoms due to disease
Must be able to take oral medication
- Patients with newly diagnosed brain stem glioma with difficulty swallowing may be eligible
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of pulmonary dysfunction or pre-existing lung disease
- No myocardial infarction within the past year
- No severe cardiac pathology
No significant ophthalmologic abnormality including, but not limited to, any of the following:
- Severe dry eye syndrome
- Keratoconjunctivitis sicca
- Sjögren's syndrome
- Severe exposure keratitis
- Any other disorder likely to increase the risk of corneal epithelial lesions
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- More than 6 weeks since prior radiotherapy
- No concurrent warfarin
- No other concurrent anticancer or investigational agents
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00360854
Locations
| Ireland | |
| Our Lady's Hospital for Sick Children Crumlin | |
| Dublin, Ireland, 12 | |
| United Kingdom | |
| 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 | |
| Great Ormond Street Hospital for Children NHS Trust | |
| London, England, United Kingdom, WC1N 3JH | |
| Middlesex Hospital | |
| London, England, United Kingdom, W1T 3AA | |
| 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 | |
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
| Investigator: | Darren Hargrave, MD | Royal Marsden NHS Foundation Trust |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00360854 History of Changes |
| Other Study ID Numbers: | CDR0000481539, CCLG-NAG-2005-09, ITCC-003, EU-20617, CCLG-CPP-05-07, ROCHE-MO18461, EUDRACT-2004-005247-10 |
| Study First Received: | August 3, 2006 |
| Last Updated: | February 6, 2009 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
untreated childhood brain stem glioma recurrent childhood cerebellar astrocytoma recurrent childhood cerebral astrocytoma recurrent childhood ependymoma recurrent childhood medulloblastoma recurrent childhood supratentorial primitive neuroectodermal tumor recurrent childhood visual pathway and hypothalamic glioma childhood central nervous system germ cell tumor childhood choroid plexus tumor childhood craniopharyngioma |
childhood grade I meningioma childhood grade II meningioma childhood grade III meningioma childhood low-grade cerebral astrocytoma childhood infratentorial ependymoma childhood supratentorial ependymoma recurrent childhood brain tumor recurrent childhood subependymal giant cell astrocytoma recurrent childhood pineoblastoma |
Additional relevant MeSH terms:
|
Brain Neoplasms Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Brain Diseases Central Nervous System Diseases Nervous System Diseases Neoplasms, Neuroepithelial |
Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Erlotinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013