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.

Condition	Treatment or Intervention	Phase
adult brain tumor	Drug: gefitinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
Maryland
      NCI - Neuro-Oncology Branch, Bethesda,  Maryland,  20892-8200,  United States; Recruiting
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0316,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-9154,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-6220,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States; Recruiting

Study chairs or principal investigators

Frank Scott Lieberman, MD,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000068984; NABTC-0001; NCT00025675
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025675
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08