Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Imatinib Mesylate in Treating Patients With Recurrent Meningioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045734
First received: September 6, 2002
Last updated: May 2, 2017
Last verified: May 2017
  Purpose
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

Condition Intervention Phase
Adult Grade I Meningioma
Adult Grade II Meningioma
Adult Grade III Meningioma
Adult Meningeal Hemangiopericytoma
Adult Meningioma
Recurrent Adult Brain Tumor
Drug: imatinib mesylate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Trial of STI571 (NSC 716051) in Patients With Recurrent Meningioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria [ Time Frame: 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:
  • Progression-free Survival According to Response Evaluation Using Macdonald Criteria [ Time Frame: 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


  • Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 [ Time Frame: Up to 5 years after completion of study treatment ]
    percentage of patients who had grade 3 or grade 4 adverse events

  • Tumor Response as Assessed by MRI Using Macdonald Criteria [ Time Frame: 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


  • Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics) [ Time Frame: 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


  • Determine Survival for Patients Treated With Imatinib Mesylate [ Time Frame: 3 years ]
    survival determined from start of treatment to date of death


Other Outcome Measures:
  • Determine Surrogate Markers of Angiogenic Peptides Using Functional Neuro-imaging and in Vitro Bioassays [ Time Frame: 5 years ]
    Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due number of patients.

  • Evidence of Platelet-derived Growth Factor (PDGF) Inhibition in Tumor Specimens [ Time Frame: - 3 years ]
    insufficient samples to allow Platelet-derived growth factor receptor (PDGFR-alpha and -beta expression to be correlated Of 22 patients only 7 samples available and only 5 yielded adequate tissue

  • Determine Correlating Molecular Abnormalities in the Tumor With Response to Treatment [ Time Frame: 3 years ]

    Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined.

    Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids.

    Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone.

    Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over Baseline (BL) if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).



Enrollment: 23
Study Start Date: February 2003
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (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

Drug: imatinib mesylate
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045734

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
University of California San Francisco
San Francisco, California, United States, 94115
United States, Maryland
National Cancer Institute Neuro-Oncology Branch
Bethesda, Maryland, United States, 20814
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Patrick Wen, MD North American Brain Tumor Consortium
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00045734     History of Changes
Obsolete Identifiers: NCT00069667
Other Study ID Numbers: NCI-2012-02495
NABTC-0108
U01CA062399 ( US NIH Grant/Contract Award Number )
CDR0000257267 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: September 6, 2002
Results First Received: March 10, 2017
Last Updated: May 2, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Meningioma
Hemangiopericytoma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017