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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Anaplastic Oligodendroglioma; Recurrent Adult Brain Tumor; Adult Glioblastoma; Adult Grade I Meningioma; Adult Anaplastic Astrocytoma; Adult Giant Cell Glioblastoma; Adult Gliosarcoma

Treatments: Other: pharmacological study; Other: laboratory biomarker analysis; Drug: erlotinib hydrochloride

Study type: Interventional

Funder types: NIH

Identifiers

NCT00045110

NCI-2012-02490 (Registry Identifier)

U01CA062399 (U.S. NIH Grant/Contract)

CDR0000256358

NABTC-01-03 (Other Identifier)

NCI-03-C-0114

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Phase 1 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.

Phase 2 I. Determine the 6-month progression-free survival (recurrent malignant glioma) II.12-month survival of patients treated with this drug (stable glioblastoma post radiation therapy)

Phase 2 - Secondary Recurrent Malignant Glioma I. Objective Tumor Response rate associated with erlotinib therapy in recurrent or progressive malignant glioma.

III. 12-month survival of patients treated with this drug Determine the safety profile of this drug in these patients. IV.. Determine the pharmacokinetics of this drug in these patients

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.

Enrollment: 136 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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136 participants in 2 patient groups

Phase 1 Dose Escalation

Experimental group

Description:

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. erlotinib hydrochloride given orally Other: pharmacological study.

Treatment:

Drug: erlotinib hydrochloride

Other: pharmacological study

Phase 2 recurrent malignant gliomas and nonprogressive GBM

Experimental group

Description:

Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day. patients requiring surgery treated 7 days prior to tumor removal (150mg/day) PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.

Treatment:

Drug: erlotinib hydrochloride

Other: pharmacological study

Other: laboratory biomarker analysis