Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria:

- Histologically confirmed glioblastoma multiforme or gliosarcoma

- Pre-therapy tumor tissue available

- Meets 1 of the following criteria:

- Patients accrued to stage 1 (closed to accrual as of 4/14/2009) or stage 1B
(opened to accrual as of 4/14/2009) must have tumors overexpressing at least 2
known dasatinib targets (i.e., SRC, KIT, PDGFR, or EPHA2)

- Patients accrued to stage 2 (closed as of 4/14/2009) do not require
overexpression of SRC, KIT, PDGFR, or EPHA2

- Prior treatment with radiotherapy and temozolomide required

- Radiographic evidence of tumor progression by MRI or CT scan

- Must be on stable or decreasing doses of corticosteroids for at least 5 days
before baseline MRI or CT scan

- Measurable disease is not required in patients who recently underwent resection
provided the following conditions are met as applicable:

- Progression of disease necessitated surgery

- Polifeprosan 20 with carmustine implants (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

- Karnofsky performance status 60-100%

- Absolute neutrophil count ≥ 1,000 cells/mm³

- Platelet count ≥ 75,000 cells/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

- WBC ≥ 3,000 cells/mm³

- Absolute lymphocyte count ≥ 500 cells/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 3 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior invasive malignancy except for nonmelanomatous skin cancer unless
disease-free for a minimum of 3 years

- No severe active comorbidity, defined as any of the following:

- Clinically significant cardiovascular disease, including any of 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 QTc > 480 msec (by Fridericia's correction)

- Ejection fraction less than institutional normal

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

- Acute bacterial or fungal infection requiring IV antibiotics

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization

- No known AIDS

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to dasatinib

- No condition that impairs the ability to swallow or retain tablets, such as the
following:

- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- No other concurrent anticancer agents or therapies

- Prior surgery for recurrent/progressive disease allowed

- Recovered from prior surgery

- More than 4 weeks since prior radiotherapy and recovered

- More than 2 weeks since prior temozolomide and recovered

- More than 2 weeks since prior and no concurrent enzyme-inducing antiepileptic drugs

- No prior therapy except radiotherapy and temozolomide

- No prior stereotactic radiosurgery or brachytherapy

- At least 7 days since prior and no concurrent potent inhibitors of CYP3A4

- At least 7 days since prior and no concurrent agents with proarrhythmic potential

- At least 7 days since prior and no concurrent antithrombotic and/or antiplatelet
agents (e.g., warfarin, heparin, low molecular weight heparin, acetylsalicylic acid,
clopidogrel, ticlopidine, or Aggrenox)

- No locally acting antacids (Maalox, Mylanta) within 2 hours before or after study
treatment

- No concurrent systemic antacids, including H2 receptor antagonist or proton pump
inhibitors

- No concurrent ibuprofen or NSAIDs

- No concurrent large quantities of grapefruit or its juice

- No concurrent potent inducers of CYP3A4

- No other concurrent investigational agents