Clinical trial NCT00045734: Imatinib Mesylate in Treating Patients With Recurrent Meningioma
Official title: Phase II Trial of STI571 (NSC 716051) in Patients With Recurrent Meningioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Grade I Meningioma
Adult Grade II Meningioma
Adult Grade III Meningioma
Adult Meningeal Hemangiopericytoma
Adult Meningioma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria
timeFrame: At 6 months
Secondary outcomes:
measure: Progression-free Survival According to Response Evaluation Using Macdonald Criteria
timeFrame: 3 years
measure: Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0
timeFrame: Up to 5 years after completion of study treatment
measure: Tumor Response as Assessed by MRI Using Macdonald Criteria
timeFrame: Up to 5 years
measure: Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics)
timeFrame: pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9
measure: Determine Survival for Patients Treated With Imatinib Mesylate
timeFrame: 3 years
Other outcomes:
measure: Determine Surrogate Markers of Angiogenic Peptides Using Functional Neuro-imaging and in Vitro Bioassays
timeFrame: 5 years
measure: Evidence of Platelet-derived Growth Factor (PDGF) Inhibition in Tumor Specimens
timeFrame: - 3 years
measure: Determine Correlating Molecular Abnormalities in the Tumor With Response to Treatment
timeFrame: 3 years
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Bethesda
country: United States
facility: National Cancer Institute Neuro-Oncology Branch
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: North American Brain Tumor Consortium
name: Patrick Wen, MD
role: PRINCIPAL_INVESTIGATOR
References: