A Phase I/II Trial of a New Tyrosine Kinase Inhibitor (Tarceva; Erlotinib Hydrochloride; OSI-774) During and After Radiotherapy in the Treatment of Patients With Newly Diagnosed High Grade Glioma and Unfavorable Low-Grade Glioma
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Trial of a New Tyrosine Kinase Inhibitor (Tarceva; Erlotinib Hydrochloride; OSI-774) During and After Radiotherapy in the Treatment of Patients With Newly Diagnosed High Grade Glioma and Unfavorable Low-Grade Glioma
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
estimate the MTD and determine the DLT of erlotinib during and after RT in children, adolescents, and young adults with newly diagnosed high-grade glioma and unfavorable low-grade glioma
Outcome Time Frame:
5 Years
Safety Issue:
Yes
Principal Investigator
Alberto Broniscer, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
St. Jude Children's Research Hospital
Authority:
United States: Food and Drug Administration
Study ID:
SJHG04
NCT ID:
NCT00124657
Start Date:
March 2005
Completion Date:
September 2015
Related Keywords:
- Brain and Central Nervous System Tumors
- adult anaplastic astrocytoma
- adult anaplastic oligodendroglioma
- adult glioblastoma
- adult giant cell glioblastoma
- adult gliosarcoma
- adult mixed glioma
- childhood mixed glioma
- untreated childhood cerebellar astrocytoma
- childhood high-grade cerebral astrocytoma
- childhood low-grade cerebral astrocytoma
- childhood oligodendroglioma
- childhood spinal cord neoplasm
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| University of California San Diego | La Jolla, California 92093 |
| Duke Children's Hospital and Health Center | Durham, North Carolina 27710 |
