Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma

St. Jude Children's Research Hospital

Status and phase: Completed; Phase 2; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: Erlotinib hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT00124657

SJHG04

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with radiation therapy and to see how well they work in treating young patients with newly diagnosed glioma.

Full description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered during and after radiotherapy in young patients with newly diagnosed high-grade glioma and unfavorable low-grade glioma.
• Determine the 1- and 2-year progression-free survival of patients treated with this regimen.

Secondary

• Determine the toxic effects of this regimen in these patients.
• Correlate genetic abnormalities in epidermal growth factor receptor (EGFR) and components of downstream pathways with treatment response in patients treated with this regimen.
• Determine the ability of erlotinib to inhibit EGFR signaling in patients with high-grade glioma who require second surgery.
• Determine the pharmacokinetics of erlotinib and its metabolites in these patients.
• Correlate plasma and cerebrospinal fluid levels of vascular endothelial growth factor and basic fibroblast growth factor with tumor response in patients treated with this regimen.
• Correlate irradiation dosimetry with patterns of failure, standard and investigational imaging, and toxicity in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of erlotinib followed by a phase II study.

• Phase I: Patients undergo radiotherapy once daily, 5 days week, for approximately 6½ weeks. Beginning on the first day of radiotherapy, patients receive oral erlotinib once daily for up to 2 years.

Cohorts of patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined.

• Phase II: Patients will receive erlotinib as in phase I at the MTD and undergo radiotherapy as in phase I.

PROJECTED ACCRUAL: A total of 75-80 patients (15-20 for the phase I portion and 60 for the phase II portion) will be accrued for this study.

Enrollment: 62 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of high-grade glioma of 1 of the following types:

  • Unfavorable low-grade glioma

    • Gliomatosis cerebri or bithalamic involvement

  • Histologically confirmed high-grade glioma (WHO grade III or IV) of 1 of the following subtypes:

    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic oligoastrocytoma
    • Anaplastic ganglioglioma
    • Pleomorphic xanthoastrocytoma with anaplastic features
    • Malignant glioneuronal tumor
    • Glioblastoma multiforme
    • Gliosarcoma

• Newly diagnosed disease

• Intracranial or spinal cord tumors allowed

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 40-100% (age 17 to 21 years) OR
• Lansky 40-100% (age 3 to 16 years)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3 (transfusion independent)
• Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• SGPT < 5 times ULN
• Albumin ≥ 2 g/dL

Renal

• Creatinine < 2 times normal OR
• Glomerular filtration rate > 70 mL/min

Cardiovascular

• No significant cardiovascular problem

Pulmonary

• No significant pulmonary problem

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No uncontrolled infection
• No significant medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior or concurrent biologic agents

Chemotherapy

• No prior or concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• No more than 42 days since prior surgery

Other

• No other prior or concurrent anticancer or experimental treatment

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 1 patient group

Patients with High-Grade/Low-Grade Glioma

Experimental group

Description:

Patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and \<26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) are not eligible for this study. Patients with spinal cord tumors will be eligible for the Phase I and Phase II component of this study, but they will not be taken into consideration to estimate PFS in the Phase II component of this trial because of their notoriously worse prognosis. Patients receive erlotinib hydrochloride.

Treatment:

Drug: Erlotinib hydrochloride