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Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jonsson Comprehensive Cancer Center, UCLA
  • UCSF Comprehensive Cancer Center
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • Hillman Cancer Center at University of Pittsburgh Cancer Institute
  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
  • University of Texas - MD Anderson Cancer Center
  • University of Texas Health Science Center at San Antonio
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
February 2, 2001
Last Updated
June 25, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00010049
Brief Title
Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma
Official Title
Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
February 27, 2001 (Actual)
Primary Completion Date
March 17, 2005 (Actual)
Study Completion Date
August 15, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
imatinib mesylate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Y. Wen, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States
Facility Name
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0316
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Hillman Cancer Center at University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9154
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-6220
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16914578
Citation
Wen PY, Yung WK, Lamborn KR, Dahia PL, Wang Y, Peng B, Abrey LE, Raizer J, Cloughesy TF, Fink K, Gilbert M, Chang S, Junck L, Schiff D, Lieberman F, Fine HA, Mehta M, Robins HI, DeAngelis LM, Groves MD, Puduvalli VK, Levin V, Conrad C, Maher EA, Aldape K, Hayes M, Letvak L, Egorin MJ, Capdeville R, Kaplan R, Murgo AJ, Stiles C, Prados MD. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res. 2006 Aug 15;12(16):4899-907. doi: 10.1158/1078-0432.CCR-06-0773.
Results Reference
result
Citation
Wen PY, Yung WKA, Lamborn K, et al.: Phase I/II study of imatinib mesylate (ST1571) for patients with recurrent malignant gliomas (NABTC 99-08). [Abstract] Neuro-Oncology 6 (4): TA-63, 385, 2004.
Results Reference
result

Learn more about this trial

Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

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