Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

NCT ID: NCT00025675

Last Updated: 2018-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-09
• Study Completion Date: 2010-01-02

Brief Summary

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

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

p450

p450 inhibitor

Group Type: ACTIVE_COMPARATOR

gefitinib

Intervention Type: DRUG

nonp450

not on p450 inhibitor

Group Type: ACTIVE_COMPARATOR

gefitinib

Intervention Type: DRUG

Interventions

gefitinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank S. Lieberman, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

NCI - Neuro-Oncology Branch

Bethesda, Maryland, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

Norden AD, Raizer JJ, Abrey LE, Lamborn KR, Lassman AB, Chang SM, Yung WK, Gilbert MR, Fine HA, Mehta M, Deangelis LM, Cloughesy TF, Robins HI, Aldape K, Dancey J, Prados MD, Lieberman F, Wen PY. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol. 2010 Jan;96(2):211-7. doi: 10.1007/s11060-009-9948-7. Epub 2009 Jun 28.

Reference Type: BACKGROUND

PMID: 19562255 (View on PubMed)

Lassman AB, Rossi MR, Raizer JJ, Abrey LE, Lieberman FS, Grefe CN, Lamborn K, Pao W, Shih AH, Kuhn JG, Wilson R, Nowak NJ, Cowell JK, DeAngelis LM, Wen P, Gilbert MR, Chang S, Yung WA, Prados M, Holland EC. 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. 2005 Nov 1;11(21):7841-50. doi: 10.1158/1078-0432.CCR-05-0421.

Reference Type: BACKGROUND

PMID: 16278407 (View on PubMed)

Other Identifiers

U01CA062399

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ABTC-0001

Identifier Type: -

Identifier Source: secondary_id

NABTC-0001

Identifier Type: -

Identifier Source: secondary_id

NABTC-0001 CDR0000068984

Identifier Type: -

Identifier Source: org_study_id