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

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00360854
• Other study ID #: CDR0000481539
• Secondary ID: CCLG-NAG-2005-09
• Status: Active, not recruiting
• Phase: Phase 1
• First received: August 3, 2006
• Last updated: September 19, 2013
• Start date: May 2005

Study information

• Verified date: June 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Brain Neoplasms
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• erlotinib hydrochloride

Genetic:
• mutation analysis

• polymorphism analysis

Other:
• laboratory biomarker analysis

• pharmacological study

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	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	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
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	Great Ormond Street Hospital for Children NHS Trust	London	England
United Kingdom	Middlesex Hospital	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

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of erlotinib hydrochloride when given alone and in combination with radiotherapy			Yes
Secondary	Dose-limiting toxicities			Yes
Secondary	Safety			Yes
Secondary	Pharmacokinetic behavior of erlotinib hydrocloride			No
Secondary	Efficacy			No
Secondary	Correlation of expression and mutations of epidermal growth factor receptor with treatment response			No