Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049127

Purpose

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of imatinib mesylate and to see how well it works in treating patients with a recurrent brain tumor that has not responded to previous surgery and radiation therapy.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: imatinib mesylate	Phase I Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Trial Of Imatinib Mesylate; (Gleevec; STI571) In Treatment Of Recurrent Oligodendroglioma And Mixed Oligoastrocytoma

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Imatinib Imatinib mesylate

U.S. FDA Resources

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

Primary Outcome Measures:

Progression-free survival (PFS) as assessed by neuroimaging and clinical evaluations at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (OS) as assessed by neuroimaging and clinical evaluations at 12 months [ Designated as safety issue: No ]
Response as assessed by neuroimaging and clinical evaluations [ Designated as safety issue: No ]
Time to progression as assessed by neuroimaging and clinical evaluations [ Designated as safety issue: No ]
PFS as assessed by neuroimaging and clinical evaluations at 12 and 24 months [ Designated as safety issue: No ]

Estimated Enrollment:	93
Study Start Date:	June 2003
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Phase II group 1 Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.	Drug: imatinib mesylate Given orally
Experimental: Phase II group 2 Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.	Drug: imatinib mesylate Given orally

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent oligodendroglioma or mixed oligoastrocytoma who are currently on enzyme-inducing anticonvulsant therapy. (Phase I)
Determine the efficacy of imatinib mesylate, as measured by response, survival, and progression-free survival, in patients with recurrent oligodendroglioma or mixed oligoastrocytoma. (Phase II)
Compare pilot data of patients who have undergone > 2 prior chemotherapy regimens for recurrent, progressive, or mixed oligodendroglioma with traditional patients with recurrent or mixed oligodendroglioma. (Phase II and pilot study)
Determine the toxicity and safety of this drug in these patients. (Phases I, II, and pilot study)
Correlate, preliminarily, 1p/19q alterations, alpha-PDFGR gene amplification, and levels of related downstream signaling elements in tumor tissue with clinical response in patients treated with this drug. (Phases I, II, and pilot study)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II and a pilot study.

Phase I: Patients receive oral imatinib mesylate twice daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate 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:
- Group 1 (concurrent enzyme-inducing anticonvulsants [EIACs]): Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
- Group 2 (non EIACs): Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.

In both groups, treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Pilot study: Patients are stratified and assigned to treatment groups as in phase II. Patients receive oral imatinib as in phase II.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 93 patients will be accrued to this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed oligodendroglioma or mixed oligoastrocytoma
- Grade 2-4
- Recurrent disease
Patients with mixed gliomas must have > 25% oligodendrogliomatous component
Failed prior surgery, radiotherapy, and temozolomide or nitrosourea-based therapy
- Progressive disease by MRI or CT scan
Measurable or evaluable disease by MRI or CT scan
More than 2 prior chemotherapy regimens for progressive or recurrent disease (pilot study only)
Currently taking anticonvulsants which can induce cytochrome p450 (e.g., phenytoin, carbamazepine, barbiturates, or primidone (Phase I only)
No prior or concurrent significant intratumoral hemorrhage

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL

Hepatic

Bilirubin no greater than 1.5 mg/dL
AST no greater than 3 times upper limit of normal

Renal

Creatinine no greater than 2.0 mg/dL

Cardiovascular

No myocardial infarction within the past 6 months
No congestive heart failure requiring maintenance therapy for life-threatening ventricular arrhythmias
No New York Heart Association class III or IV heart disease

Other

No active uncontrolled infection
No other severe concurrent disease that would preclude study or interfere significantly with interpreting potential drug-induced toxic effects
No other active malignancy except nonmelanoma skin cancer
No concurrent serious immunocompromised status unless related to concurrent steroids
HIV-positive patients allowed
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 2 weeks since prior biologic noncytotoxic agents (e.g., thalidomide or interferon)
No concurrent biologic therapy or immunotherapy for brain cancer

Chemotherapy

See Disease Characteristics
No prior interstitial chemotherapy, including carmustine wafers, unless separate lesion seen on MRI outside of prior treatment field
At least 2 weeks since prior vincristine
At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas)
No concurrent chemotherapy for brain cancer

Endocrine therapy

At least 2 weeks since prior tamoxifen
Concurrent corticosteroids allowed if dose stable for at least 1 week prior to study entry
No concurrent hormonal therapy for brain cancer

Radiotherapy

See Disease Characteristics
At least 12 weeks since prior radiotherapy
No prior stereotactic radiosurgery or interstitial brachytherapy unless separate lesion seen on MRI outside of prior treatment field
No concurrent radiotherapy for brain cancer

Surgery

See Disease Characteristics
At least 2 weeks since prior surgery for initial or progressive disease and recovered
No concurrent surgery for brain cancer

Other

At least 2 weeks since prior isotretinoin
At least 4 weeks since prior investigational agents
No concurrent therapeutic warfarin or heparin
- Low-dose warfarin and heparin (1 mg daily) allowed
No other concurrent investigational or noninvestigational therapy for brain cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049127

Show 126 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Kurt A. Jaeckle, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier:	NCT00049127 History of Changes
Other Study ID Numbers:	CDR0000257812, NCCTG-N0272
Study First Received:	November 12, 2002
Last Updated:	March 15, 2011
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult anaplastic oligodendroglioma
recurrent adult brain tumor
adult mixed glioma
adult oligodendroglioma

Additional relevant MeSH terms:

Brain Neoplasms
Nervous System Neoplasms
Oligodendroglioma
Central Nervous System Neoplasms
Astrocytoma
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial

Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012