Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00010049

Collaborator

National Cancer Institute (NCI) (NIH)

105

Enrollment

Locations

65.5

Actual Duration (Months)

9.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an effective treatment for recurrent glioma and meningioma.

PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate in treating patients who have progressive, recurrent, or unresectable malignant glioma or meningioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: imatinib mesylate	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent malignant glioma or meningioma.
Determine the safety profile of this drug in these patients.
Determine the pharmacokinetics of this drug, with or without concurrent enzyme-inducing anti-epileptic drugs (EIAEDs), in these patients. (Stratum of patients currently taking EIAEDs closed to accrual as of 05/15/2003 for phase I and phase II)
Determine angiogenic activity in vivo using functional neuro-imaging studies and in vitro with assays of serum angiogenic peptides.
Determine the efficacy of this drug, in terms of 6-month progression-free survival and objective tumor response, in these patients.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drug use (yes [stratum closed to accrual as of 05/15/2003 for phase I and phase II] vs no).

Phase I (patients with glioma or meningioma) Patients in cohorts 1 and 2 receive oral imatinib mesylate (STI571) once daily on days 1-28. Patients in cohorts 3-5 receive oral STI571 twice daily on days 1 and 3-28 of the first course and on days 1-28 of subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of STI571 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.

Phase II (patients with glioma) (glioblastoma multiforme patients excluded as of 05/15/2003) Patients receive oral STI571 at the MTD determined in phase I, 1-2 times daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study within 6 months and a total of 39 patients will be accrued for phase II of the study within 6-8 months. (Glioblastoma multiforme patients excluded from phase II as of 05/13/2003).

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas

Actual Study Start Date :

Feb 27, 2001

Actual Primary Completion Date :

Mar 17, 2005

Actual Study Completion Date :

Aug 15, 2006

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 recurrent or unresectable malignant glioma
Glioblastoma multiforme (phase I only)
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic mixed oligoastrocytoma
Malignant astrocytoma not otherwise specified
Gliosarcoma
Low-grade histology with subsequent diagnosis of malignant glioma allowed (phase I only) OR
Histologically confirmed recurrent or unresectable benign or malignant meningioma (phase I only)
No prior intracranial hemorrhage
Failed prior radiotherapy
Progressive or recurrent disease by MRI or CT scan and/or resection
PET or thallium scan, MR spectroscopy, or surgical documentation required in patients who have received prior interstitial brachytherapy or stereotactic radiosurgery
Stable dose of steroids for 5-7 days prior to MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

More than 8 weeks

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

Bilirubin less than 2 times upper limit of normal (ULN)
SGOT less than 2 times ULN
No significant hepatic disease

Renal:

Creatinine less than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
No significant renal disease

Cardiovascular:

No significant cardiac disease
No deep venous or arterial thrombosis within the past 6 weeks

Pulmonary:

No pulmonary embolism within the past 6 weeks

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for up to 6 months after study participation
No other serious concurrent medical illness
No serious active infection
No concurrent disease that would obscure toxicity or alter drug metabolism
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior interferon or thalidomide and recovered
No concurrent immunotherapy
No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy:

Recovered from prior chemotherapy
At least 4 weeks since prior cytotoxic therapy
At least 2 weeks since prior vincristine
At least 6 weeks since prior nitrosoureas
At least 4 weeks since prior temozolomide
At least 3 weeks since prior procarbazine
Prior polifeprosan 20 with carmustine implant (Gliadel wafer) allowed
Prior radiosensitizers allowed
No other concurrent chemotherapy
Phase I only:
Prior chemotherapy required for anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic mixed oligoastrocytoma
Prior treatment for up to 3 relapses allowed
Phase II only:
Prior chemotherapy not required
Prior treatment for up to 2 relapses allowed

Endocrine therapy:

See Disease Characteristics
At least 1 week since prior tamoxifen and recovered
No concurrent anticancer hormonal therapy

Radiotherapy:

See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery:

See Disease Characteristics
Recovered from prior surgical resection of recurrent or progressive disease

Other:

At least 1 week since prior non-cytotoxic agents and recovered
At least 1 week since prior tretinoin and recovered
At least 2 weeks since prior drugs that affect hepatic metabolism
No other concurrent investigational agents
No concurrent warfarin

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	48109-0316
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
8	Simmons Cancer Center at University of Texas Southwestern Medical 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