Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045110
First received: September 6, 2002
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Grade I Meningioma
Adult Grade II Meningioma
Adult Grade III Meningioma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
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 OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) or erlotinib hydrochloride defined as the dose at which fewer than one-third of patients experience DLT (phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Summarized by descriptive statistics.

  • Progression-free survival (phase II) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Response rate (complete or partial response) graded using RECIST criteria [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Toxicity described based on the CTC severity grading [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Summarized by descriptive statistics.


Enrollment: 36
Study Start Date: August 2002
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (erlotinib hydrochloride)

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.

Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant glioma or recurrent or progressive meningioma.

II. Determine the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. IV. 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.

  Eligibility

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

Inclusion Criteria:

  • 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
  • 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
  • Measurable or evaluable disease
  • Performance status - Karnofsky 60-100%
  • More than 8 weeks
  • 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)
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • SGOT less than 1.5 times ULN
  • Creatinine less than 1.5 mg/dL
  • 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
  • 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
  • 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
  • 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
  • At least 1 week since prior tamoxifen
  • 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
  • Recovered from prior surgery
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045110

Locations
United States, Massachusetts
North American Brain Tumor Consortium
Watertown, Massachusetts, United States, 02472
Sponsors and Collaborators
Investigators
Principal Investigator: Lauren Abrey North American Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00045110     History of Changes
Obsolete Identifiers: NCT00055276
Other Study ID Numbers: NCI-2012-02490, NCI-2012-02490, NCI-03-C-0114, CDR0000256358, NABTC-01-03, NABTC-01-03, U01CA062399
Study First Received: September 6, 2002
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 27, 2014