Temozolomide and Lapatinib Ditosylate in Treating Patients with Recurrent Low-Grade Ependymoma

Inclusion Criteria

• Histologically proven ependymoma or anaplastic ependymoma; there must be pathologic or imaging confirmation of tumor progression or regrowth; the patients histologic diagnosis must be confirmed on central pathology review prior to registration step 2
• The patient must have at least 1 block of tissue available or 15 unstained slides at a minimum, for central pathology review and molecular profiling of the tissue sample
• History and physical examination, including neurologic examination, within 2 weeks prior to registration
• Patients must be able to undergo brain or spine magnetic resonance imaging (MRI) scans with intravenous gadolinium, based on tumor location(s) within 14 days prior to registration
• Patients must be on a steroid dose that has been stable or decreasing for at least 5 days; if the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required
• Karnofsky performance status >= 70
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin (Hgb) >= 10.0 gm/dL (Note: the use of transfusion or other intervention to achieve Hgb >= 10.0 is acceptable)
• White blood cell count (WBC) >= 3,000/mcL
• Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times the upper limit of normal
• Bilirubin =< 1.6 mg/dL
• Creatinine < 1.7 mg/dL
• Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of: * 28 days from the administration of any investigational agent * 28 days from administration of prior cytotoxic therapy with the following exceptions: ** 14 days from administration of vincristine ** 42 days from administration of nitrosoureas ** 21 days from administration of procarbazine * 7 days from administration of non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. [radiosensitizer does not count]) * 28 days from prior radiation therapy
• Patients must have recovered from the effects of surgery and a minimum of 14 days must have elapsed from the day of surgery to the day of registration; for core or needle biopsy, a minimum of 7 days must have elapsed prior to registration
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study; to best assess the extent of residual disease post-operatively, an MRI should be done no later than 96 hours in the immediate postoperative period or at least 4 weeks postoperatively, within 14 days prior to registration; if the "within 96-hour of surgery" scan is more than 14 days before registration, the scan needs to be repeated
• Patients must sign study-specific informed consent and authorization for the release of their protected health information prior to registration; patients must be registered in the prior to treatment with study drug
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration
• Women of childbearing potential and male participants must practice adequate contraception
• All patients must have an left ventricular ejection fraction (LVEF) measurement of at least 50% by echocardiogram (ECHO) or multigated acquisition scan (MUGA) (if clinically indicated) within 14 days prior to registration; the method used for LVEF assessment in an individual subject must be the same throughout the trial

Exclusion Criteria

• Prior invasive malignancy that is not the ependymoma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years
• Transmural myocardial infarction or unstable angina within 3 months prior to study registration
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to registration
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
• History of stroke or transient ischemic attack within 3 months prior to registration
• Inadequately controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 90 mmHg despite antihypertensive medication)
• History of cerebral vascular accident (CVA) within 3 months prior to registration
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
• Patients cannot be receiving HAART (highly active anti-retroviral therapy) therapy
• Pregnant or nursing women
• Any condition that impairs ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease)
• Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs) nor any other cytochrome P450 3A4 (CYP3A4) inducers such as rifampin or St. John’s wort beginning at least 14 days prior to registration step 2
• Patients cannot be receiving CYP3A4 inhibitors beginning at least 7 days prior to registration step 2
• Patients must not have current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)