Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 64
- Locations
- 188
- Primary Endpoint
- Number of Patients Achieving 6-month Progression-free Survival (6mPFS)
Overview
Brief 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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)
Arms & Interventions
Treatment (dasatinib)
Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
Intervention: Dasatinib (Drug)
Treatment (dasatinib)
Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
Intervention: Pharmacological Study (Other)
Outcomes
Primary Outcomes
Number of Patients Achieving 6-month Progression-free Survival (6mPFS)
Time Frame: Registration to 6 months
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.
Secondary Outcomes
- Number of Patients Achieving Objective Response (Partial or Complete Response) OR 6-month Progression-free Survival (6mPFS)(Registration to 6 months)
- Overall Survival(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(From registration to 6 months)
- Rate of Adverse Events(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.))
- Progression-free Survival(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(From registration to 6 months)
- Correlation of Pharmacokinetic Data With Dosing, Toxicity, and Efficacy(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.))