Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of CNS tumors. PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have recurrent or progressive CNS tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of gefitinib in patients with recurrent or progressive supratentorial malignant gliomas or brain or spinal meningiomas receiving enzyme-inducing antiepileptic drugs (EIAEDs). (Phase I of the study closed to accrual as of 09/19/2003). Determine the toxic effects of this drug in these patients. Determine the pharmacokinetics of this drug in patients receiving EIAEDs. Determine the efficacy of this drug in terms of 6-month progression-free survival of these patients. Determine the safety profile of the phase II dose of this drug in these patients. OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no) and disease type (for phase II only) (benign meningioma vs malignant meningioma vs hemangiopericytoma vs glioblastoma vs other anaplastic glioma). (Phase I closed to accrual as of 09/19/2003). Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients (who are receiving EIAEDs) receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 2 weeks. PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for the phase I portion of this study within 10 months . (Phase I closed to accrual as of 09/19/2003). A total of 48 patients will be accrued for the phase II portion of this study within 6-8 months.

Official Title
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ZD1839 FOR Treatment Of Recurrent Or Progressive Malignant Astrocytoma Or Glioblastoma And Recurrent Or Progressive Meningioma: A Phase II Study With A Phase I Component For Patients Receiving EIAEDs

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Histologically confirmed supratentorial malignant primary glioma Glioblastoma multiforme Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma not otherwise specified Histologically confirmed or radiographically defined recurrent or progressive brain or spinal meningioma, including base of skull or cavernous sinus meningiomas Benign, malignant, or atypical May include neurofibromatosis type I or II Hemangiopericytoma allowed Recurrent or progressive disease by MRI or CT scan Evidence of true progressive disease by PET or thallium scan, MR spectroscopy, or surgical documentation required if patient received prior interstitial brachytherapy or stereotactic radiosurgery (to the target lesion for meningioma and hemangiopericytoma) Steroid dosage must be stable for at least 5 days prior to scan No limitations on the number of prior surgeries, radiotherapy or chemotherapy regimens, or radiosurgery treatments for patients with meningioma or hemangiopericytoma and may include standard external beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery in any combination Patients with glioma must have failed prior radiotherapy Original histology of low-grade glioma allowed if subsequent confirmation of malignant glioma is made at time of recurrence Phase I (closed to accrual as of 09/19/2003): Prior treatment for no more than 3 prior relapses in patients with glioma Phase II: Measurable disease after prior surgical resection of recurrent or progressive disease Prior treatment for no more than 2 prior relapses in patients with glioma 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 120,000/mm^3 Hemoglobin at least 10 g/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 OR Creatinine clearance at least 60 mL/min Cardiovascular: No significant cardiac risk factors within the past 6 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No gastrointestinal risk factors (e.g., active ulcerative colitis) within the past 6 months No active infection No concurrent disease that would obscure toxicity or dangerously alter drug metabolism No other significant medical illness that would preclude study No other malignancy within the past 3 years except non-melanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior interferon or thalidomide No concurrent filgrastim (G-CSF) Chemotherapy: See Disease Characteristics At least 2 weeks since prior vincristine At least 6 weeks since prior nitrosoureas At least 3 weeks since prior procarbazine Endocrine therapy: At least 1 week since prior tamoxifen Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics At least 7 days since prior surgery for recurrent or progressive tumor and recovered Other: Recovered from prior therapy No prior gefitinib or other epidermal growth factor receptor inhibitor At least 1 week since prior isotretinoin At least 1 week since other prior noncytotoxic agents (except radiosensitizers) At least 4 weeks since prior investigational agents Concurrent low-molecular weight heparin or warfarin for deep vein thrombosis or pulmonary embolism allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: p450<br>p450 inhibitor | Drug: gefitinib<br> <br> |
| Active Comparator: nonp450<br>not on p450 inhibitor | Drug: gefitinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 6 months |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult meningioma, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult pilocytic astrocytoma, adult subependymoma, adult mixed glioma, adult meningeal hemangiopericytoma, adult grade III meningioma, adult giant cell glioblastoma, adult gliosarcoma, adult grade I meningioma, adult grade II meningioma