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

NCT ID: NCT00360854

Last Updated: 2013-09-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

erlotinib hydrochloride

Intervention Type: DRUG

mutation analysis

Intervention Type: GENETIC

polymorphism analysis

Intervention Type: GENETIC

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Cancer and Leukaemia Group

OTHER

Sponsor Role: lead

Principal Investigators

Darren Hargrave, MD

Role:

Royal Marsden NHS Foundation Trust

Locations

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Leicester Royal Infirmary

Leicester, England, United Kingdom

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Middlesex Hospital

London, England, United Kingdom

Great Ormond Street Hospital for Children NHS Trust

London, England, United Kingdom

Central Manchester and Manchester Children's University Hospitals NHS Trust

Manchester, England, United Kingdom

Sir James Spence Institute of Child Health

Newcastle upon Tyne, England, United Kingdom

Queen's Medical Centre

Nottingham, England, United Kingdom

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Southampton University Hospital NHS Trust

Southampton, England, United Kingdom

Royal Marsden NHS Foundation Trust - Surrey

Sutton, England, United Kingdom

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Countries

Ireland; United Kingdom

Other Identifiers

CCLG-NAG-2005-09

Identifier Type: -

Identifier Source: secondary_id

ITCC-003

Identifier Type: -

Identifier Source: secondary_id

EU-20617

Identifier Type: -

Identifier Source: secondary_id

CCLG-CPP-05-07

Identifier Type: -

Identifier Source: secondary_id

ROCHE-MO18461

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2004-005247-10

Identifier Type: -

Identifier Source: secondary_id

CDR0000481539

Identifier Type: -

Identifier Source: org_study_id