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A Phase I/II Trial Of OSI-774 In Patients With Recurrent Malignant Gliomas And Malignant Gliomas Post Radiation Therapy

Phase 1/Phase 2
18 Years
Open (Enrolling)
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

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Trial Information

A Phase I/II Trial Of OSI-774 In Patients With Recurrent Malignant Gliomas And Malignant Gliomas Post Radiation Therapy


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

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.

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

- Abnormal corneal sensitivity test (Schirmer test or similar tear production

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) or erlotinib hydrochloride defined as the dose at which fewer than one-third of patients experience DLT (phase I)

Outcome Description:

Summarized by descriptive statistics.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Lisa DeAngelis

Investigator Role:

Principal Investigator

Investigator Affiliation:

North American Brain Tumor Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

August 2002

Completion Date:

Related Keywords:

  • 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
  • Astrocytoma
  • Brain Neoplasms
  • Glioblastoma
  • Glioma
  • Meningioma
  • Oligodendroglioma
  • Gliosarcoma



North American Brain Tumor Consortium Watertown, Massachusetts  02472