Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas

Inclusion Criteria

• Ability to provide written informed consent prior to participation in the study and any related procedures being performed.
• Participants must have agreed to and signed an authorization for the release of their protected health information.
• Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must have a life expectancy of at least 8 weeks.
• Patients greater than 18 years of age.
• Histologically documented diagnosis of proven glioblastoma (GBM), or anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic mixed oligoastrocytoma (AMO). Patients are eligible if the original local pathology was lower-grade glioma. Pathology will be read centrally to confirm diagnosis.
• Documentation of amplified PDGFRA by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative PCR from tumor tissue (=>3 copy number). Availability of unstained paraffin slides or the paraffin block of pretreatment baseline tissue is required for eligibility and for molecular analysis and would help to identify molecular predictors of outcome (all patients).
• Participants must have a Karnofsky Performance Status (KPS) ≥ 60.
• Adequate end organ function, defined as the following:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• White blood cell (WBC) count ≥ 3.0 x 109/L
• Biochemistry:
• AST/SGOT and ALT/SGPT ≤ 2.5 x institution's ULN
• Total bilirubin ≤ 1.5 x institution's ULN
• Serum creatinine ≤ 1.5 x institution's ULN or 24-hour creatinine clearance ≥ 50 ml/min
• Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related
• Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication.
• Potassium (WNL)
• Magnesium (WNL)
• Phosphorous (WNL)
• Calcium (WNL)
• Coagulation studies:
• INR 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
• Myocardial infarction within 1 year of starting study drug
• Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
• Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of CYP3A4 inhibitors (http://medicine.iupui.edu/clinpharm/ddis/table.asp)
• Patient currently receiving treatment with any medications that have the potential to prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. See link for a comprehensive list of agents that prolong the QT interval (http://www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm).
• Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
• Acute or chronic pancreatic disease.
• Another malignancy that is clinically significant or requires active intervention (chemotherapy or radiation)
• Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, active or uncontrolled infection).
• Acute or chronic liver or severe renal disease
• History of significant congenital or acquired bleeding disorder.
• Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
• Treatment with other investigational agents within 30 days of Day 1.
• History of non-compliance to medical regimens or inability to grant consent.