Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Active	18 and over	NCI	NCCTG-N0272 N0272, NCT00049127

Objectives

1. 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)
2. 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)
3. 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)
4. Determine the toxicity and safety of this drug in these patients. (Phases I, II, and pilot study)
5. 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)

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Progression-free survival (PFS) as assessed by neuroimaging and clinical evaluations at 6 months

Overall survival (OS) as assessed by neuroimaging and clinical evaluations at 12 months
Response as assessed by neuroimaging and clinical evaluations
Time to progression as assessed by neuroimaging and clinical evaluations
PFS as assessed by neuroimaging and clinical evaluations at 12 and 24 months

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.

Wen PY, Yung WK, Lamborn KR, et al.: Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res 12 (16): 4899-907, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Kurt Jaeckle, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

U.S.A.
Florida
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Illinois
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3019
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Clive
	Medical Oncology and Hematology Associates - West Des Moines
		Robert Behrens	Ph:  515-875-9713
	Des Moines
	CCOP - Iowa Oncology Research Association
		Robert Behrens	Ph:  515-244-7586 888-244-6061
	John Stoddard Cancer Center at Iowa Lutheran Hospital
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Lutheran Hospital	Ph:  515-241-8704
	John Stoddard Cancer Center at Iowa Methodist Medical Center
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Methodist Medical Center	Ph:  515-241-6727
	Medical Oncology and Hematology Associates at John Stoddard Cancer Center
		Robert Behrens	Ph:  515-282-2921
	Medical Oncology and Hematology Associates at Mercy Cancer Center
		Robert Behrens	Ph:  515-643-8740
	Mercy Cancer Center at Mercy Medical Center - Des Moines
		Robert Behrens	Ph:  515-643-8206 888-221-4849
	Mason City
	Mercy Cancer Center at Mercy Medical Center - North Iowa
		Clinical Trials Office - Mercy Cancer Center at Mercy Medical Center - North Iowa	Ph:  641-422-6304
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-0088
Kansas
	Anthony
	Hospital District Sixth of Harper County
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Chanute
	Cancer Center of Kansas, PA - Chanute
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Dodge City
	Cancer Center of Kansas, PA - Dodge City
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	El Dorado
	Cancer Center of Kansas, PA - El Dorado
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Fort Scott
	Cancer Center of Kansas - Fort Scott
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Independence
	Cancer Center of Kansas-Independence
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Kingman
	Cancer Center of Kansas, PA - Kingman
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Lawrence
	Lawrence Memorial Hospital
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Liberal
	Southwest Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Newton
	Cancer Center of Kansas, PA - Newton
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Parsons
	Cancer Center of Kansas, PA - Parsons
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Pratt
	Cancer Center of Kansas, PA - Pratt
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Salina
	Cancer Center of Kansas, PA - Salina
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wellington
	Cancer Center of Kansas, PA - Wellington
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wichita
	Associates in Womens Health, PA - North Review
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Medical Arts Tower
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	CCOP - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Via Christi Cancer Center at Via Christi Regional Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Winfield
	Cancer Center of Kansas, PA - Winfield
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
Michigan
	Adrian
	Hickman Cancer Center at Bixby Medical Center
		Clinical Trials Office - Hickman Cancer Center at Bixby Medical Center	Ph:  517-265-0116
	Ann Arbor
	CCOP - Michigan Cancer Research Consortium
		Philip Stella, MD	Ph:  734-712-1000
	Saint Joseph Mercy Cancer Center
		Philip Stella, MD	Ph:  734-712-1000
	Grosse Pointe Woods
	Van Elslander Cancer Center at St. John Hospital and Medical Center
		Clincial Trials Office - Van Elslander Cancer Center at St. John Hospital and Medical Center	Ph:  313-343-3166
	Lambertville
	Haematology-Oncology Associates of Ohio and Michigan, PC
		Paul Schaefer, MD	Ph:  419-479-5605
	Monroe
	Community Cancer Center of Monroe
		Paul Schaefer, MD	Ph:  419-479-5605
	Mercy Memorial Hospital - Monroe
		Paul Schaefer, MD	Ph:  419-479-5605
Minnesota
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Duluth
	CCOP - Duluth
		Daniel Nikcevich, MD, PhD	Ph:  218-786-3625
	Duluth Clinic Cancer Center - Duluth
		Clinical Trials Office - Duluth Clinic Cancer Center - Duluth	Ph:  218-786-3308
	Miller - Dwan Medical Center
		Daniel Nikcevich, MD, PhD	Ph:  218-786-3625
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Hutchinson
	Hutchinson Area Health Care
		Daniel Anderson	Ph:  320-234-5000 800-454-3903
	Maplewood
	HealthEast Cancer Care at St. John's Hospital
		Daniel Anderson	Ph:  651-232-7970
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Hennepin County Medical Center - Minneapolis
		Clinical Trials Office - Hennepin County Medical Center - Minneapolis	Ph:  612-873-5911
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Ph:  763-520-1893
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Saint Louis Park
	CCOP - Metro-Minnesota
		Patrick Flynn, MD	Ph:  612-863-8585
	Park Nicollet Cancer Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Saint Paul
	United Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Shakopee
	St. Francis Cancer Center at St. Francis Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	St. Paul
	Regions Hospital Cancer Care Center
		Clinical Trials Office - Regions Hospital Cancer Care Center	Ph:  651-254-1517
	Waconia
	Ridgeview Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Woodbury
	Minnesota Oncology Hematology, PA - Woodbury
		Patrick Flynn, MD	Ph:  612-863-8585
Montana
	Billings
	Billings Clinic - Downtown
		Clinical Trials Office - Billings Clinic - Downtown	Ph:  800-996-2663
			Email: research@billingsclinic.org
	CCOP - Montana Cancer Consortium
		Benjamin Marchello, MD	Ph:  406-238-6290
	Hematology-Oncology Centers of the Northern Rockies - Billings
		Benjamin Marchello, MD	Ph:  406-238-6290
	Northern Rockies Radiation Oncology Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	St. Vincent Healthcare Cancer Care Services
		Benjamin Marchello, MD	Ph:  406-238-6290
	Bozeman
	Bozeman Deaconess Cancer Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	Butte
	St. James Healthcare Cancer Care
		Benjamin Marchello, MD	Ph:  406-238-6290
	Great Falls
		Benjamin Marchello, MD	Ph:  406-238-6290
	Great Falls Clinic - Main Facility
		Benjamin Marchello, MD	Ph:  406-238-6290
	Havre
	Northern Montana Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290
	Helena
	St. Peter's Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell
	Glacier Oncology, PLLC
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell Medical Oncology at KRMC
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell Regional Medical Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	Missoula
	Community Medical Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	Guardian Oncology and Center for Wellness
		Benjamin Marchello, MD	Ph:  406-238-6290
	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
		Clinical Trials Office - Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Ph:  406-329-7029
	Montana Cancer Specialists at Montana Cancer Center
		Clinical Trials Office - Montana Cancer Specialists at Montana Cancer Center	Ph:  406-238-6962
Nebraska
	Omaha
	Alegant Health Cancer Center at Bergan Mercy Medical Center
		Clinical Trials Office - Alegant Health Cancer Center at Bergen Mercy Medical Center	Ph:  402-398-6060
	CCOP - Missouri Valley Cancer Consortium
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
	Creighton University Medical Center
		Clinical Trials Office - Creighton University Medical Center	Ph:  402-280-4100
	Immanuel Medical Center
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
North Dakota
	Bismarck
	Bismarck Cancer Center
		Edward Wos, DO	Ph:  701-323-5741
	Medcenter One Hospital Cancer Care Center
		Edward Wos, DO	Ph:  701-323-5741
	Mid Dakota Clinic, PC
		Clinical Trials Office - Mid Dakota Clinic, PC	Ph:  701-530-6950
	St. Alexius Medical Center Cancer Center
		Clinical Trials Office - St. Alexius Medical Center Cancer Center	Ph:  701-530-6950
Ohio
	Bowling Green
	Wood County Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Clyde
	North Coast Cancer Care - Clyde
		Paul Schaefer, MD	Ph:  419-479-5605
	Elyria
	Hematology Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Lima
	Lima Memorial Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Maumee
	Northwest Ohio Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Luke's Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Oregon
	St. Charles Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic - Oregon
		Paul Schaefer, MD	Ph:  419-479-5605
	Sandusky
	North Coast Cancer Care, Incorporated
		Paul Schaefer, MD	Ph:  419-479-5605
	Sylvania
	Flower Hospital Cancer Center
		Clinical Trials Office - Flower Hospital Cancer Center	Ph:  419-824-1842
	Tiffin
	Mercy Hospital of Tiffin
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo
	CCOP - Toledo Community Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Medical University of Ohio Cancer Center
		Clinical Trials Office - Medical University of Ohio Cancer Center	Ph:  419-383-6583
	St. Anne Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Vincent Mercy Medical Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic, Incorporated - Main Clinic
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Hospital
		Clinical Trials Office - Toledo Hospital	Ph:  419-824-1842
	Wauseon
	Fulton County Health Center
		Clinical Trials Office - Fulton County Health Center	Ph:  419-330-2708
Pennsylvania
	Allentown
	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
		Suresh Nair, MD	Ph:  610-402-0512
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Clinical Trials Office - Geisinger Cancer Institute	Ph:  570-271-5251
	Hazleton
	Geisinger Hazleton Cancer Center
		Albert Bernath, MD	Ph:  570-214-9290
	State College
	Geisinger Medical Group - Scenery Park
		Albert Bernath, MD	Ph:  570-214-9290
	Wilkes-Barre
	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
		Clinical Trials Office - Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Ph:  570-271-5251
Virginia
	Fredericksburg
	Fredericksburg Oncology, Incorporated
		Paul Schaefer, MD	Ph:  419-479-5605
Wyoming
	Sheridan
	Welch Cancer Center at Sheridan Memorial Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290

Registry Information
Official Title		Phase I/II Trial Of Imatinib Mesylate; (Gleevec; STI571) In Treatment Of Recurrent Oligodendroglioma And Mixed Oligoastrocytoma
Trial Start Date		2003-06-20
Trial Completion Date		2008-12-17 (estimated)
Registered in ClinicalTrials.gov		NCT00049127
Date Submitted to PDQ		2002-09-05
Information Last Verified		2009-11-22
NCI Grant/Contract Number		CA25224

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