Gefitinib Plus Temozolomide in Treating Patients With Malignant Primary Glioma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00027625

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

45.1

Actual Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining gefitinib with temozolomide in treating patients who have malignant primary glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: gefitinib Drug: temozolomide	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of gefitinib when given in combination with temozolomide in patients with malignant primary glioma.
Determine the toxic effects of this regimen in these patients.
Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gefitinib. Patients are stratified according to use of concurrent enzyme-inducing anti-epileptic drugs (yes vs no).

Patients receive oral gefitinib once daily on days 1-35 and oral temozolomide once daily on days 8-12 for the first course only. For the second and subsequent courses, patients receive oral gefitinib once daily on days 1-28 and oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 1 year and then every 3-6 months thereafter.

PROJECTED ACCRUAL: Approximately 3-42 patients will be accrued for this study within 1-14 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of ZD 1839 And Temozolomide For The Treatment Of Gliomas

Actual Study Start Date :

Jan 28, 2002

Actual Primary Completion Date :

Mar 17, 2005

Actual Study Completion Date :

Nov 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed malignant primary glioma
Glioblastoma multiforme
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic mixed oligoastrocytoma
Malignant astrocytoma not otherwise specified
Stable or progressive disease
Progressive disease after interstitial brachytherapy or stereotactic radiosurgery must be confirmed by positron emission tomography or thallium scan, magnetic resonance spectroscopy, or surgical biopsy
Prior treatment for no more than 3 prior relapses allowed

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

More than 8 weeks

Hematopoietic:

WBC greater than 3,000/mm^3
Absolute neutrophil count greater than 1,500/mm^3
Platelet count greater than 120,000/mm^3
Hemoglobin greater than 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 greater than 60 mL/min

Other:

Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
No active infection
No other concurrent significant medical illness that would preclude study participation
No significant gastrointestinal risk factors (e.g., active ulcerative colitis) within the past 6 months
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
No concurrent filgrastim (G-CSF) during the first course of study therapy

Chemotherapy:

At least 2 weeks since prior vincristine
At least 3 weeks since prior procarbazine
At least 6 weeks since prior nitrosoureas
Prior or concurrent temozolomide allowed if there is no evidence of progression while receiving therapy

Endocrine therapy:

At least 1 week since prior tamoxifen
Must be on a stable dose of corticosteroids for at least 5 days

Radiotherapy:

See Disease Characteristics
At least 3 weeks since prior radiotherapy

Surgery:

See Disease Characteristics
At least 1 week since prior surgical resection

Other:

Recovered from all prior therapy
No prior gefitinib
At least 1 week since prior non-cytotoxic agents except radiosensitizers
At least 4 weeks since prior cytotoxic therapy
At least 4 weeks since prior investigational agents
At least 3 years since prior therapy for other malignancy
Concurrent therapeutic agents allowed at stable dosage
Concurrent enzyme-inducing anti-epileptic drugs allowed if continued during study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143-0128
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
4	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
8	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75390-9154
9	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
10	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-6220
11	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792