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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00124657
First received: July 26, 2005
Last updated: December 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: Erlotinib hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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 [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
  • estimate the 1- and 2-year PFS of children, adolescents, and young adults with intracranial anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) treated with a combination of maximum safe surgical resection, local RT, and erlotinib (Tarceva) [ Time Frame: 5 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the toxicities associated with the chronic use of erlotinib in these patients [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To analyze the EGFR and some of the components of downstream pathways for specific genetic abnormalities (e.g., amplification, mutation), and to investigate their influence on treatment response [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who require second surgery [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To prospectively investigate the correlation between standard (magnetic resonance imaging [MRI]) and investigational (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) radiologic techniques in assessing tumor response to this treatment [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To prospectively investigate the technical factors involved in planning and administering conformal fractionated RT as outlined in this study, and to correlate RT dosimetry with patterns of failure, standard and investigational imaging and toxicity [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To identify genomic regions of gains and losses and to perform a global analysis of gene expression in pediatric high-grade glioma. Based on our results, validation studies are also planned. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: March 2005
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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).
Other Names:
  • Tarceva
  • OSI-774
  • NSC#718781

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00124657

Locations
United States, California
University of California San Diego
San Diego, California, United States, 92123-4282
United States, North Carolina
Duke Children's Hospital and Health Center
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Alberto Broniscer, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00124657     History of Changes
Other Study ID Numbers: SJHG04
Study First Received: July 26, 2005
Last Updated: December 4, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
childhood spinal cord neoplasm
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 oligodendroglioma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Glioma
Nervous System Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014