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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


Phase 1/Phase 2
3 Years
21 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

Thank you

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 HospitalMemphis, Tennessee  38105-2794
University of California San DiegoLa Jolla, California  92093
Duke Children's Hospital and Health CenterDurham, North Carolina  27710