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Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma
This study has been completed.
Sponsors and Collaborators: North American Brain Tumor Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00045110
  Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Phase I
Phase II

MedlinePlus related topics: Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I/II Trial Of OSI-774 In Patients With Recurrent Malignant Gliomas And Malignant Gliomas Post Radiation Therapy

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) (phase I) [ Designated as safety issue: Yes ]
  • Progression-free survival (phase II) at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival at 1 year and continuously [ Designated as safety issue: No ]
  • Radiographic response every 2 months [ Designated as safety issue: No ]

Study Start Date: August 2002
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant glioma or recurrent or progressive meningioma.
  • Determine the safety profile of this drug in these patients.
  • Determine the pharmacokinetics of this drug in these patients.
  • Determine the 6-month progression-free survival, 12-month survival, and objective tumor response of patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to study phase (I vs II), concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no), histology (recurrent GBM vs recurrent anaplastic glioma vs recurrent meningioma vs stable GBM), preoperative candidacy (yes vs no), and concurrent steroids (yes vs no).

  • Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are treated with erlotinib as above at the phase II dose. Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose.

Patients are followed for survival.

PROJECTED ACCRUAL: Approximately 36 patients will be accrued for the phase I portion of this study within 1 year. Approximately 117-122 patients (32 recurrent glioblastoma multiforme [GBM], 20 recurrent anaplastic gliomas, 55 stable post-radiotherapy GBM, and 10-15 recurrent meningioma) will be accrued for the phase II portion of this study within 15 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Histologically confirmed intracranial malignant glioma

      • Glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma not otherwise specified
      • Original histology of low-grade glioma allowed provided a subsequent histology of malignant glioma is confirmed
    • Histologically or radiographically confirmed recurrent or progressive benign or malignant meningioma
  • Progressive disease or tumor recurrence on MRI or CT scan

    • Phase I: No more than 3 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
    • Phase II: No more than 2 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens NOTE: *Including polifeprosan 20 with carmustine implants (Gliadel wafers)
  • Patients with progressive disease must have failed prior radiotherapy* that was completed at least 4 weeks ago

    • Patients with progressive disease between 4 and 12 weeks after completion of external beam radiotherapy must have clear evidence of progression on MRI
    • Patients with GBM who have completed external beam radiotherapy and do not show progression are eligible
    • Patients with progressive disease after interstitial brachytherapy or stereotactic radiosurgery must have confirmed true progression rather than radiation necrosis based upon positron-emission tomography, thallium scanning, MRI, or surgical documentation NOTE: *Prior radiotherapy is not required for patients with meningioma
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • More than 8 weeks

Hematopoietic

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 mg/dL (transfusion allowed)

Hepatic

  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • SGOT less than 1.5 times ULN

Renal

  • Creatinine less than 1.5 mg/dL

Ophthalmic

  • None of the following ophthalmic abnormalities:

    • Abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
    • Congenital abnormality (e.g., Fuch's dystrophy)
    • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
    • Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Patients found to have dry eyes on examination but have an otherwise normal examination allowed

Other

  • No active infection
  • No other serious concurrent medical illness
  • No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No other disease that would obscure toxicity or dangerously alter drug metabolism
  • No significant medical illness that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 12 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • At least 1 week since prior thalidomide
  • At least 1 week since prior interferon
  • At least 4 weeks since prior SU5416 or other experimental biologic agents

Chemotherapy

  • See Disease Characteristics
  • No prior chemotherapy (including polifeprosan 20 with carmustine implant [Gliadel wafers]) for patients with stable GBM
  • At least 2 weeks since prior vincristine
  • At least 3 weeks since prior procarbazine
  • At least 6 weeks since prior nitrosoureas

Endocrine therapy

  • At least 1 week since prior tamoxifen

Radiotherapy

  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No more than 6 weeks since prior external beam radiotherapy for patients with GBM without evidence of progression

Surgery

  • Recovered from prior surgery

Other

  • Recovered from prior therapy
  • At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) except radiosensitizers
  • At least 4 weeks since prior cytotoxic therapy
  • At least 4 weeks since prior tipifarnib or imatinib mesylate
  • No prior erlotinib or other epidermal growth factor receptor inhibitors
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00045110

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0316
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Simmons Cancer Center at University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-9154
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
North American Brain Tumor Consortium
Investigators
Principal Investigator: Lauren E. Abrey, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Lisa M. DeAngelis, MD Memorial Sloan-Kettering Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: CDR0000256358, NABTC-0103, NCI-03-C-0114
Study First Received: September 6, 2002
Last Updated: November 21, 2008
ClinicalTrials.gov Identifier: NCT00045110  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
adult mixed glioma
recurrent adult brain tumor
adult grade III meningioma
adult giant cell glioblastoma
adult gliosarcoma
adult grade I meningioma
adult grade II meningioma

Study placed in the following topic categories:
Erlotinib
Glioblastoma
Meningeal Neoplasms
Astrocytoma
Central Nervous System Neoplasms
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Oligodendroglioma
Meningioma
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Enzyme Inhibitors
Neoplasms, Neuroepithelial
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009