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

Alternate Title

Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	ABTC-0001 NABTC-0001, NCT00025675, NABTC-00-01

Objectives

1. 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).
2. Determine the toxic effects of this drug in these patients.
3. Determine the pharmacokinetics of this drug in patients receiving EIAEDs.
4. Determine the efficacy of this drug in terms of 6-month progression-free survival of these patients.
5. Determine the safety profile of the phase II dose of this drug in these patients.

Entry 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

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

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 120,000/mm³
• 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

Expected Enrollment

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.

Outcomes

Progression-free survival at 6 months

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.

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

Frank Lieberman, MD, Protocol chair		Ph: 412-692-2600 Email: liebermanf@upmc.edu

Registry Information
Official Title		ZD1839 FOR Treatment Of Recurrent Or Progressive Malignant Astrocytoma Or Glioblastoma And Recurrent Or Progessive Meningioma: A Phase II Study With A Phase I Component For Patients Receiving EIAEDs
Trial Start Date		2002-01-03
Trial Completion Date		2009-06-02
Registered in ClinicalTrials.gov		NCT00025675
Date Submitted to PDQ		2001-08-29
Information Last Verified		2005-05-04
NCI Grant/Contract Number		U01-CA62399

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