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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
Est. completion date
Est. primary completion date
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


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
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