Sunitinib in Treating Patients With Recurrent Malignant Gliomas

Inclusion Criteria

• Stratum 1:
• Currently not receiving an enzyme-inducing anticonvulsant
• Patients receiving non-enzyme inducing anticonvulsants are eligible for this stratum
• Histologically confirmed WHO grade IV astrocytoma (glioblastoma multiforme [GBM]) including gliosarcoma
• Stratum 2 (USA patients only):
• Currently on stable dose of an enzyme-inducing anticonvulsant (with confirmed therapeutic serum levels) for at least 2 weeks prior to study registration including any of the following:
• Phenytoin
• Carbamazepine
• Phenobarbital
• Histologically confirmed grade IV astrocytoma (GBM), gliosarcoma, grade III astrocytoma, oligodendroglioma, or mixed oligoastrocytoma
• All patients must have unequivocal evidence of tumor progression by MRI or CT scan performed no longer than 14 days prior to study registration
• Patients undergoing surgery for progressive disease with nonmeasurable disease on post-operative MRI, ideally obtained within 48 hours of surgery, (i.e., macroscopic gross total resection) are eligible
• ECOG performance status 0-2 (Karnofsky ≥ 60%)
• Life expectancy > 3 months
• Leukocytes ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 9 g/dL
• Serum calcium ≤ 12.0 mg/dL
• Total bilirubin within normal institutional limits (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN
• Creatinine = 500 msec), serious ventricular arrhythmia (VT or VF > 3 beats in a row) or other significant ECG abnormalities are excluded
• Patients with poorly controlled hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) are ineligible
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib malate tablets are excluded
• Patients with any of the following conditions are excluded:
• Serious or non-healing wound, ulcer, or bone fracture
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
• History of myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, or coronary or peripheral artery bypass graft or stenting within 12 months prior to study entry
• Class III or IV heart failure as defined by the NYHA functional classification system
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections requiring antibiotics or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
• Pregnant women are excluded from this study
• Breastfeeding should be discontinued if the mother is treated with sunitinib malate
• Patients are eligible if they received up to 1 previous chemotherapy regimen
• ≥ 12 weeks must have elapsed from the completion of radiation therapy
• ≥ 4 weeks from previous non-nitrosoureas-based cytotoxic chemotherapy
• ≥ 6 weeks from any nitrosoureas
• ≥ 2 weeks from last cytostatic chemotherapy such as erlotinib hydrochloride or tamoxifen
• Patients who have undergone previous stereotactic radiosurgery, intratumoral chemotherapy, or brachytherapy are eligible if functional imaging (PET or SPECT scan, MR spectroscopy, or dynamic MRI) supports the diagnosis of recurrent tumor or recurrent disease is confirmed histologically
• Concurrent steroids allowed provided the patients is on a stable or decreasing dose for at least 7 days prior to baseline tumor assessment (MRI and/or CT scan)
• Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, or VEGF Trap) are ineligible
• Patients who require use