Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	NABTC-0103 NCI-03-C-0114, NCT00045110, NABTC-01-03

Objectives

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

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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.

Outcomes

Maximum tolerated dose (MTD) (phase I)
Progression-free survival (phase II) at 6 months

Overall survival at 1 year and continuously
Radiographic response every 2 months

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.

Norden AD, Raizer JJ, Abrey LE, et al.: Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol : , 2009.[PUBMED Abstract]

Lassman AB, Rossi MR, Raizer JJ, et al.: Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res 11 (21): 7841-50, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North American Brain Tumor Consortium

Lauren Abrey, MD, Principal investigator		Ph: 212-639-5122; 800-525-2225 Email: abreyl@mskcc.org
Lisa DeAngelis, MD, Principal investigator		Ph: 212-639-7997; 800-525-2225

Registry Information
Official Title		A Phase I/II Trial Of OSI-774 In Patients With Recurrent Malignant Gliomas And Malignant Gliomas Post Radiation Therapy
Trial Start Date		2002-08-14
Trial Completion Date		2008-11-18
Registered in ClinicalTrials.gov		NCT00045110
Date Submitted to PDQ		2002-06-28
Information Last Verified		2005-11-29
NCI Grant/Contract Number		CA62399

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