Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00010049
First received: February 2, 2001
Last updated: July 31, 2010
Last verified: December 2003
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: imatinib mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas

Resource links provided by NLM:


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

Study Start Date: November 2002
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00010049

Locations
United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0128
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0316
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9154
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
North American Brain Tumor Consortium
Investigators
Study Chair: Patrick Y. Wen, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00010049     History of Changes
Obsolete Identifiers: NCT00023179
Other Study ID Numbers: CDR0000068437, NABTC-9908, NCI-01-C-0243, UCLA-0101024
Study First Received: February 2, 2001
Last Updated: July 31, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult brain tumor
adult meningioma
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult pilocytic astrocytoma
adult subependymoma
adult grade III meningioma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioma
Meningioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Neoplasms by Site
Nervous System Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014