Safety Study of Afatinib for Brain Cancer

Inclusion Criteria: * Diagnosis 1. Dose Escalation Cohorts: Histologically confirmed diagnosis of brain cancer: 1. glioblastoma (GBM), 2. anaplastic astrocytoma (AA), 3. anaplastic oligodendroglioma (AO), 4. anaplastic mixed oligoastrocytoma (AMO), 5. low grade gliomas, 6. brain metastases, 7. meningiomas, 8. leptomeningeal metastases 9. chordomas 10. pituitary tumors 11. medulloblastomas 2. Expansion Cohort: Histologically confirmed diagnosis of high-grade glioma with altered EGFR (e.g., amplification, mutation), including: 1. glioblastoma (GBM), 2. anaplastic astrocytoma (AA), 3. anaplastic oligodendroglioma (AO), 4. anaplastic mixed oligoastrocytoma (AMO) * Has failed prior standard therapy including maximal safe surgical resection (when appropriate for the specific cancer type), radiation therapy (when appropriate for the specific cancer type), and systemic therapy (when appropriate for the specific cancer type). * For diagnosis of GBM: has undergone maximal safe surgical resection, a course of postoperative radiation therapy with concurrent temozolomide, and maintenance temozolomide. * For diagnosis of meningioma: has no other option of standard therapy such as surgical resection (partial or total resection) or radiation. * Age 18 years and older. * Karnofsky Performance Status ≥ 60%. * Adequate organ function, defined as all of the following: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. 2. Platelet count ≥ 100 x 109/L. 3. Hemoglobin ≥ 9.0 g/dL. 4. Total Bilirubin ≤ 1.5 institution's upper limit of normal (ULN). 5. Aspartate amino transferase (AST) ≤ 2.5 x institution's ULN. 6. Alanine amino transferase (ALT) ≤ 2.5 x institution's ULN. 7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related. * Recovered from any previous therapy-related toxicity to Grade 1 or to their clinical baseline at study entry. * Women of child-bearing potential has negative serum or urine pregnancy test before the initiation of study drug dosing. Exclusion Criteria: * Insufficient time from prior therapy to study entry: 1. less than 28 days from whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS); 2. less than 28 days from any investigational agent; 3. less than 28 days from prior cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine (for GBM: 14 days from irinotecan or topotecan), 42 days from nitrosoureas, 21 days from procarbazine, irinotecan or topotecan administration); 4. less than 14 days from hormonal treatment 5. less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. 6. When radiation necrosis is suspected, standard of care confirmatory imaging, such as MRI perfusion, magnetic resonance (MR) spectroscopy and or PET will be performed, and patients with findings consistent with radiation necrosis will be excluded. * Current or anticipated use of enzyme-inducing anti-epileptic drugs (EIAED). * Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study. * Known hypersensitivity to afatinib or its excipients. * History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3 or 4, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months prior to enrollment. * Pregnant, nursing, or not using acceptable method of birth control. * Any history of or concomitant condition that would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug. * Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. * Known pre-existing interstitial lung disease. * Known active hepatitis B infection (defined as presence of Hep B sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier. * Prior participation in a blinded afatinib clinical study, even if not assigned to afatinib treatment.