Imatinib Mesylate in Treating Patients With Recurrent Meningioma

Phase 2

Completed

Conditions: Adult Meningioma
Adult Meningeal Hemangiopericytoma
Adult Grade II Meningioma
Adult Grade I Meningioma
Adult Grade III Meningioma
Recurrent Adult Brain Tumor

Interventions: Drug: imatinib mesylate
Other: laboratory biomarker analysis
Other: pharmacological study

Registration Number: NCT00045734

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent meningioma. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth

Detailed Description: PRIMARY OBJECTIVE:

I. Determine the efficacy of imatinib mesylate, in terms of 6-month progression-free survival, of patients with recurrent meningioma.

SECONDARY OBJECTIVES I. Determine the response rate and overall survival of patients treated with this drug.

II. Evaluate the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. IV. Develop exploratory data concerning surrogate markers of of angiogenic activity in vivo using functional neuro-imaging studies and in vitro assays of serum angiogenic peptides of this drug in these patients.

V. Develop exploratory data concerning evidence of platelet-derived growth factor (PDGF) inhibition in tumor specimens taken from patients undergoing surgery VI. Develop exploratory data correlating molecular abnormalities in the tumor with response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes vs no), histology (benign vs atypical or malignant), neurofibromatosis positivity (yes vs no), and preoperative candidacy (yes vs no).

Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 8-12 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Histologically confirmed meningioma
- Benign, malignant, or atypical disease
- Neurofibromatosis (NF) type 1 or 2 allowed
- Hemangiopericytoma allowed
Unequivocal evidence of tumor recurrence or progression by MRI or CT scan (on steroid dosage that is stable for at least 5 days)
Evaluable residual disease by MRI or CT scan if previously treated with surgical resection for recurrent or progressive disease
Newly diagnosed recurrent disease that requires surgical debulking allowed
Prior standard external-beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery allowed provided disease has progressed since completion of therapy
- Patients who have had prior brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon positron-emission tomography or thallium scanning, magnetic resonance spectroscopy, or surgical documentation
Patients with a history of NF may have other stable Central Nervous System (CNS) tumors (e.g., schwannoma, acoustic neuroma, or ependymoma) provided those lesions have been stable in size for the past 6 months
Performance status - Karnofsky 60-100%
More than 8 weeks
Absolute neutrophil count at least 2,000/mm^3
Platelet count at least 120,000/mm^3
Hemoglobin at least 10 g/dL (transfusions allowed)
No bleeding disorders
Bilirubin less than 2 times upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) less than 2 times ULN
Prothrombin Time (PT), Partial thromboplastin time (PTT), and International normalized Ratio (INR) no greater than 1.5 times ULN
Creatinine less than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
No deep venous or arterial thrombosis within the past 6 weeks
No pulmonary embolism within the past 6 weeks
No serious active infection
No prior intracranial hemorrhage
No concurrent disease that would obscure toxicity or dangerously alter drug metabolism
No other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix unless the patient is in complete remission and off all therapy for that disease for at least 3 years
No other significant medical illness that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after study participation
At least 1 week since prior interferon or thalidomide
No concurrent immunotherapy
Concurrent epoetin alfa allowed
At least 4 weeks since prior cytotoxic chemotherapy
At least 2 weeks since prior vincristine
At least 6 weeks since prior nitrosoureas
At least 3 weeks since prior hydroxyurea or procarbazine
No concurrent chemotherapy
At least 1 week since prior tamoxifen
No concurrent hormonal therapy
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy
Recovered from prior surgery
Recovered from all prior therapy
At least 1 week since prior noncytotoxic therapy (e.g., isotretinoin) except radiosensitizers
At least 2 weeks since prior drugs that affect hepatic metabolism
At least 4 weeks since prior investigational agents
No concurrent warfarin (heparin or low-molecular weight heparin allowed)
No other concurrent investigational agents
No concurrent acetaminophen of more than 500 mg/day
No other concurrent anticancer therapy

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (imatinib mesylate)	imatinib mesylate	Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis
Treatment (imatinib mesylate)	laboratory biomarker analysis	Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis
Treatment (imatinib mesylate)	pharmacological study	Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis

Primary Outcome Measures

Name	Time	Method
6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria	At 6 months	The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (magnetic resonance imaging \[MRI\]) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration

Secondary Outcome Measures

Name	Time	Method
Determine Survival for Patients Treated With Imatinib Mesylate	3 years	survival determined from start of treatment to date of death
Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0	Up to 5 years after completion of study treatment	percentage of patients who had grade 3 or grade 4 adverse events
Progression-free Survival According to Response Evaluation Using Macdonald Criteria	3 years	The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration
Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics)	pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9	Blood collected before and at 1,2,4 ad 24 hours after ingestion of imatinib on day 8 of cycle 1 result is the measurement of the before dosing on day 8 (trough level) and the 24 hour dosing day 8
Tumor Response as Assessed by MRI Using Macdonald Criteria	Up to 5 years	The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration

Trial Locations

Locations (7): University of California Los Angeles
🇺🇸
Los Angeles, California, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
National Cancer Institute Neuro-Oncology Branch
🇺🇸
Bethesda, Maryland, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States

Imatinib Mesylate in Treating Patients With Recurrent Meningioma

Recruitment & Eligibility

Study & Design

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