Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

Adult Glioblastoma Clinical Trial

Official title:

Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423735
• Other study ID #: NCI-2009-00744
• Secondary ID: NCI-2009-00744CD
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2007
• Est. completion date: September 4, 2018

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well dasatinib works in treating patients with glioblastoma multiforme or gliosarcoma that has come back. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. To determine the therapeutic efficacy of dasatinib in all patients (i.e., stages 1B and 2 combined) with recurrent/progressive glioblastoma (GBM) as measured by 6-month progression-free survival.

SECONDARY OBJECTIVES:

I. To determine the therapeutic efficacy of dasatinib for stage 1B patients with recurrent/progressive GBM as measured by a hybrid endpoint of 6-month progression-free survival OR objective response of (complete response [CR] or partial response [PR]) rate.

II. To determine patient overall survival. III. To determine the toxicity of dasatinib in the treatment of patients with GBM.

IV. To determine radiographic response rate to treatment. V. To determine patient progression-free survival. VI. To explore molecular correlates of clinical outcome. VII. To explore pharmacokinetic correlates of dosing, toxicity, and efficacy.

OUTLINE:

Patients receive dasatinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.

After the completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: September 4, 2018
• Est. primary completion date: March 9, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven diagnosis of GBM; gliosarcoma is also an eligible diagnosis

• The patient must consent to submission of tissue for central pathology review

• Patients who have already undergone central pathology review through their enrollment on another Radiation Therapy Oncology Group (RTOG) GBM trial do not need to consent to having their material re-reviewed by the central pathologist for this study

• All patients must consent to molecular analysis of pre-dasatinib tumor tissue

• Patients accrued to stage I (closed to accrual) or stage IB (opened to accrual May 5, 2009) must have tumors overexpressing at least 2 known dasatinib targets (i.e., SRC proto-oncogene, non-receptor tyrosine kinase [SRC], v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [KIT], platelet-derived growth factor receptor [PDGFR], or ephrin type-A receptor 2 [EPHA2])

• Patients accrued to stage II (cohort closed; not currently applicable) do not require overexpression of SRC, KIT, PDGFR, or EPHA2

• History and physical examination, including height and weight, within 10 days prior to registration on study

• Brain magnetic resonance imaging (MRI) with and without gadolinium within 10 days prior to registration on study

• Contrast-enhanced computed tomography (CT) scans are allowed for patients who cannot undergo MRI scanning

• Karnofsky performance status >= 60

• Absolute neutrophil count (ANC) >= 1,000 cells/mm^3

• Platelets >= 75,000 cells/mm^3

• Hemoglobin (Hgb) >= 8.0 g/dl; (note: the use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable)

• Leukocytes >= 3,000 cells/mm^3

• Absolute lymphocyte count (ALC) >= 500 cells/mm^3

• Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional upper limit of normal

• Creatinine =< 3 X institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• All patients must have undergone prior treatment with radiotherapy and temozolomide; no other prior treatments are allowed

• There must be unequivocal radiographic evidence for tumor progression by MRI or CT scan, and the same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement; patients must be on a stable or decreasing dose of corticosteroids for at least 5 days before the baseline MRI/CT is performed

• Patients having undergone recent surgery for recurrent/progressive disease are eligible as long as they have recovered from the effects of surgery; patients who recently underwent resection without measurable disease post-operatively are also eligible

• Measurable disease is not required for eligibility in patients who recently underwent resection as long as the following conditions are met as applicable:

• Progression of disease led to the surgery

• Gliadel wafers were not placed during the most recent surgery

• Neither convection enhanced delivery nor catheters for infusion of chemotherapy were used during the most recent surgery

• Radioactive seeds were not placed during the most recent surgery

• The histology of the most recent surgery documented recurrent/persistent/progressive malignant glioma

• Women of childbearing potential must have a negative beta human chorionic gonadotropin (B HCG) pregnancy test =< 3 days prior to registration

• Patient must sign study-specific informed consent prior to study entry

Exclusion Criteria:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

• Radiotherapy within 4 weeks or temozolomide within 14 days prior to registration or failure to recover from adverse events of either radiotherapy or temozolomide

• Patients may not be receiving any other investigational agents

• Severe, active comorbidity, defined as follows:

• Any clinically significant cardiovascular disease including the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months

• Transmural myocardial infarction or ventricular tachyarrhythmia within the past 6 months

• Prolonged corrected QT interval (QTc) > 480 msec (Fridericia correction)

• Ejection fraction less than institutional normal

• Major conduction abnormality (unless a cardiac pacemaker is present)

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; breastfeeding should be discontinued if the mother is treated with dasatinib

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib

• Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible

• Patients must not be taking hepatic enzyme inducing antiepileptic drugs (EIAEDs); if patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for >= 2 weeks prior to initiation of dasatinib

• Patients who require antacids should use short-acting, locally active agents (e.g., Maalox, Mylanta etc.); however, these agents should not be taken within either 2 hours before or 2 hours after the dasatinib dose

• Use of antithrombotic and/or antiplatelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, clopidogrel, ticlopidine, Aggrenox)

• Use of ibuprofen or non-steroidal anti-inflammatory drugs (NSAIDs)

• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded

• Prior treatment with stereotactic radiosurgery (including Gamma-Knife, Cyberknife, or other variants) or brachytherapy

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Brain Neoplasms
• Glioblastoma
• Gliosarcoma
• Recurrent Adult Brain Neoplasm

Intervention

Drug:
• Dasatinib
Given PO

Other:
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Boston Medical Center	Boston	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Aultman Health Foundation	Canton	Ohio
United States	Cape Radiation Oncology	Cape Girardeau	Missouri
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Veteran Affairs Medical Center	Dayton	Ohio
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Glendale Adventist Medical Center	Glendale	California
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	M D Anderson Cancer Center	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network-Southside Cancer Center	Jacksonville	Florida
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida
United States	Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire
United States	Kettering Medical Center	Kettering	Ohio
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Thompson Cancer Survival Center - West	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Sparrow Hospital	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Upper Delaware Valley Cancer Center	Milford	Pennsylvania
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Intermountain Medical Center	Murray	Utah
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Thompson Cancer Survival Center at Methodist	Oak Ridge	Tennessee
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	21st Century Oncology-Orange Park	Orange Park	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	Bay Medical Center	Panama City	Florida
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Renown Regional Medical Center	Reno	Nevada
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Highland Hospital	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Mercy General Hospital Radiation Oncology Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Salem Hospital	Salem	Oregon
United States	UH Seidman Cancer Center at Salem Regional Medical Center	Salem	Ohio
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Arizona Oncology Services Foundation	Scottsdale	Arizona
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas
United States	Sparta Cancer Treatment Center	Sparta	New Jersey
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Saint John's Hospital	Springfield	Illinois
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Upper Valley Medical Center	Troy	Ohio
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	University Pointe	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cancer Treatment Center	Wooster	Ohio
United States	Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	WellSpan Health-York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology, Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Achieving 6-month Progression-free Survival (6mPFS)	This study utilized a two-stage phase II design (Stage 1B and 2). The primary endpoint of 6-month progression-free survival (6mPFS) would be assessed based on the patients combined from 1B and 2 if the study continued to Stage 2. Null hypothesis = 11%; alternative hypothesis = 25%. Simon's minmax 2-stage design was used with type I and type II error both set at 10%. If the first stage met its criteria (see secondary outcome measure), then accrual would continue, otherwise there would be no further accrual and the alternative hypothesis would be rejected. Following Stage 2 accrual completion and 6 months of follow-up, if 9 or more patients were alive without progression by 6 months, the null hypothesis would be rejected in favor of the alternative.	Registration to 6 months
Secondary	Number of Patients Achieving Objective Response (Partial or Complete Response) OR 6-month Progression-free Survival (6mPFS)	Study design and efficacy determination uses the hybrid endpoint of 6mPFS or complete/partial response of any duration prior to or at 6 months. Null hypothesis = 11%; alternative hypothesis = 25%. Simon's minmax 2-stage design was used with type I and type II error both set at 10%. Stage 1 and 1B: If 2 or fewer patients were alive and progression-free at 6 months or achieved complete/partial response, then there would be no further accrual and the alternative hypothesis would be rejected. Otherwise accrual would continue to a total of 50 analyzable patients to address the primary endpoint. Complete Response: Complete disappearance of all enhancing tumor on consecutive CT or MRI scans at least 1 month apart; off corticosteroids; neurologically stable/improved. Partial Response: = 50% decrease in size of enhancing tumor on consecutive CT or MRI scans at least 1 month apart; corticosteroids stable/reduced; neurologically stable/improved.	Registration to 6 months
Secondary	Overall Survival	Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. The study is not designed for a comparison of the treatment arms to each other.	Analysis occurs after all patients have been on study for at least 6 months. (Patients are followed from registration to death or study termination whichever occurs first.)
Secondary	Treatment Response Rates at Six Months	Best response is assessed using standard criteria for patients with malignant gliomas (Macdonald 1990) as reported by the site. Complete response (CR): Complete disappearance of all enhancing tumor on consecutive CT or MRI scans at least 1 month apart; off corticosteroids; neurologically stable/improved. Partial response (PR): = 50% decrease in size of enhancing tumor on consecutive CT or MRI scans at least 1 month apart; corticosteroids stable/reduced; neurologically stable/improved. Stable disease (SD): Does not qualify for CR, PR, or PD. Progressive disease (PD): = 25% increase in the size of enhancing tumor or any new tumor; neurologically worse; steroids stable/increased. The best tumor response is defined as the best radiographic response for patients evaluable for radiographic response prior to progression, up to six months. The study is not designed for a comparison of the treatment arms to each other.	From registration to 6 months
Secondary	Progression-free Survival	Progression-free survival time is measured from randomization to the date of first progression or death, else the last follow-up date on which the patient was reported alive, and is estimated by the Kaplan-Meier method. Progression is defined as = 25% increase in the size of enhancing tumor or any new tumor, neurologically worse, or steroids stable/increased. The study is not designed for a comparison of the treatment arms to each other.	Analysis occurs after all patients have been on study for at least 6 months. (Patients are followed from registration to death or study termination whichever occurs first.)
Secondary	Rate of Adverse Events	The rate of patients' worst overall grade of adverse event is reported. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. The study is not designed for a comparison of the treatment arms to each other.	Analysis occurs after all patients have been on study for at least 6 months. (Patients are followed from registration to death or study termination whichever occurs first.)
Secondary	Correlation of Molecular Markers and Tumor Response	The following markers were examined: p-SRC, PDGFR, EPHA2, c-KIT. Patients were categorized based on the number of positive molecular markers they had: 2 vs. 3 and 4. Correlation of marker category and best tumor response was tested using Fisher's exact test. The best tumor response is defined as the best radiographic response for patients evaluable for radiographic response prior to progression up to six months. Patients are combined from the two treatment arms.	From registration to 6 months
Secondary	Correlation of Pharmacokinetic Data With Dosing, Toxicity, and Efficacy	Sufficient pharmacokinetic data was not obtained.	Analysis occurs after all patients have been on study for at least 6 months. (Patients are followed from registration to death or study termination whichever occurs first.)