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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Given PO
Correlative studies
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.
Time frame: Registration to 6 months
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.
Time frame: Registration to 6 months
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.
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Mobile Infirmary Medical Center
Mobile, Alabama, United States
Arizona Oncology Services Foundation
Scottsdale, Arizona, United States
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, United States
Mercy San Juan Medical Center
Carmichael, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Glendale Adventist Medical Center
Glendale, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, United States
...and 178 more locations
Time frame: 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.)
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.
Time frame: From registration to 6 months
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.
Time frame: 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.)
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.
Time frame: 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.)
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.
Time frame: From registration to 6 months
Correlation of Pharmacokinetic Data With Dosing, Toxicity, and Efficacy
Sufficient pharmacokinetic data was not obtained.
Time frame: 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.)