Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00025675

Collaborator

National Cancer Institute (NCI) (NIH)

105

Enrollment

Locations

Arms

98.8

Actual Duration (Months)

8.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Oct 9, 2001

Actual Primary Completion Date :

Jul 5, 2006

Actual Study Completion Date :

Jan 2, 2010

Arms and Interventions

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

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 [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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