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

NCT ID: NCT00124657

Last Updated: 2015-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2014-09-30

Brief Summary

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.

Detailed 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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with High-Grade/Low-Grade Glioma

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.

Group Type: EXPERIMENTAL

Erlotinib hydrochloride

Intervention Type: DRUG

This study has 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib will be given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study is 120mg/m2 per day (maximum dose of 200mg per day).

Interventions

Erlotinib hydrochloride

This study has 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib will be given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study is 120mg/m2 per day (maximum dose of 200mg per day).

Intervention Type: DRUG

Other Intervention Names

Tarceva; OSI-774; NSC#718781

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rady Children's Hospital, San Diego

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alberto Broniscer, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

University of California San Diego

San Diego, California, United States

Duke Children's Hospital and Health Center

Durham, North Carolina, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

SJHG04

Identifier Type: -

Identifier Source: org_study_id