Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00010049
• Other study ID #: NABTC-9908
• Secondary ID: CDR0000068437NCI
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 27, 2001
• Est. completion date: August 15, 2006

Study information

• Verified date: June 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Other known NCT identifiers

• NCT00023179

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: August 15, 2006
• Est. primary completion date: March 17, 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Meningioma
• Nervous System Neoplasms

Intervention

Drug:
• imatinib mesylate

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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, — View 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.