Imatinib Mesylate in Treating Patients With Recurrent Meningioma

Phase II Trial of STI571 (NSC 716051) in Patients With Recurrent Meningioma

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

Study Overview

• Status: Completed
• Conditions: Recurrent Adult Brain Tumor; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Meningeal Hemangiopericytoma; Adult Meningioma; Adult Grade III Meningioma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: imatinib mesylate

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • San Francisco, California, United States, 94115
      • University of California San Francisco
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • National Cancer Institute Neuro-Oncology Branch
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: imatinib mesylate; Given orally; Other Names: Gleevec; CGP 57148; Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria	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	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival According to Response Evaluation Using Macdonald Criteria	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	3 years
Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0	percentage of patients who had grade 3 or grade 4 adverse events	Up to 5 years after completion of study treatment
Tumor Response as Assessed by MRI Using Macdonald Criteria	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	Up to 5 years
Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics)	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	pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9
Determine Survival for Patients Treated With Imatinib Mesylate	survival determined from start of treatment to date of death	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Surrogate Markers of Angiogenic Peptides Using Functional Neuro-imaging and in Vitro Bioassays	Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due number of patients.	5 years
Evidence of Platelet-derived Growth Factor (PDGF) Inhibition in Tumor Specimens	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	- 3 years
Determine Correlating Molecular Abnormalities in the Tumor With Response to Treatment	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).	3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Patrick Wen, MD, North American Brain Tumor Consortium

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Disease Attributes; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Neoplasms, Fibrous Tissue; Recurrence; Meningioma; Hemangiopericytoma; Solitary Fibrous Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-02495; U01CA062399 (U.S. NIH Grant/Contract); NABTC-0108; CDR0000257267 (Registry Identifier: PDQ (Physician Data Query))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO