Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

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ClinicalTrials.gov Identifier: NCT00025675

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : June 26, 2018

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: gefitinib	Phase 2

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	105 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	October 9, 2001
Actual Primary Completion Date :	July 5, 2006
Actual Study Completion Date :	January 2, 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Gefitinib

Genetic and Rare Diseases Information Center resources: Glioma Glioblastoma Gliosarcoma Oligodendroglioma Brain Tumor, Adult Meningioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Hemangiopericytoma Pilocytic Astrocytoma Subependymoma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: p450 p450 inhibitor	Drug: gefitinib
Active Comparator: nonp450 not on p450 inhibitor	Drug: gefitinib

Outcome Measures

Primary Outcome Measures :

Progression-free survival at 6 months [ Time Frame: 6 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 120 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00025675

Locations


United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
NCI - Neuro-Oncology Branch
Bethesda, Maryland, United States, 20892-8200
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0316
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9154
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

National Cancer Institute (NCI)

Investigators


Study Chair:	Frank S. Lieberman, MD	University of Pittsburgh

More Information

Publications:

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.

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. Erratum in: Clin Cancer Res. 2006 Jan 1;12(1):322. Razier, Jeffrey R [corrected to Raizer, Jeffrey J].


Responsible Party:	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier:	NCT00025675 History of Changes
Other Study ID Numbers:	NABTC-0001 CDR0000068984 U01CA062399 ( U.S. NIH Grant/Contract ) ABTC-0001 NABTC-0001
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	June 26, 2018
Last Verified:	June 2018

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:


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

Additional relevant MeSH terms:


Glioblastoma Astrocytoma Nervous System Neoplasms Central Nervous System Neoplasms Meningioma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases Neoplasms, Vascular Tissue Meningeal Neoplasms Gefitinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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