The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.

The Study Drugs:

Temozolomide is designed to kill cancer cells by damaging deoxyribonucleic acid (DNA) (the genetic material of cells). This could cause the tumor cells to die.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the human epidermal growth factor receptor 2 (Her2/neu) receptor and the epidermal growth factor receptor (EGFR).

Study Drug Administration:

If you are found to be eligible to take part in this study, every day, you will take lapatinib by mouth once a day in the morning. You should take lapatinib 1 hour before or 1 hour after eating, with at least 1 cup (about 8 oz.) of water.

On Days 1-7 and 15-21 of each cycle, you will take temozolomide by mouth 1 time each day. You will start to take a lower dose of temozolomide for the first 2 cycles, then take a higher dose for Cycles 3 and beyond if you tolerate the treatment. It should be taken at least 2 hours before and 2 hours after eating with 1 cup (about 8 oz.) of water.

You should swallow temozolomide and/or lapatinib whole, one right after the other, without chewing either of the study drugs. If you vomit while taking temozolomide and lapatinib, you cannot take more capsules before the next scheduled dose. You should report any missed pills or trouble you have with taking the pills to your study doctor. Your study doctor will give you a form (patient diary) to fill out to keep track of your treatment. You will be asked to return your completed diary and pill bottles at each visit with your doctor.

Each study "cycle" is 28 days.

Study Visits:

Every 2 weeks, blood (about 2-3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot.

Every 8 weeks, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your vital signs.
• You will have a neurological exam.
• Your performance status will be recorded.
• You will be asked about any drugs you may be taking and if you have experienced any side effects.
• You will complete the quality of life questionnaire.
• You will have an magnetic resonance imaging (MRI) scan to check the status of the disease.
• You will have either a multi-gated acquisition scan (MUGA) scan (if the doctor thinks it is needed) or an echocardiogram.

Length of Study:

You will be on study treatment for up to 2 years. You will be taken off study treatment early if the disease gets worse or you experience intolerable side effects.

After you are off study, you may be able to continue taking lapatinib for as long as the doctor thinks it is in your best interest. Your doctor will discuss this with you.

End-of-Study Visit:

After you go off study treatment, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam.
• Your performance status will be recorded.
• You will be asked about any drugs you may be taking and if you have experienced any side effects.
• You will have a neurological exam.
• Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot.
• You will complete the questionnaire.
• You will have an MRI scan to check the status of the disease.
• You will have either a MUGA scan (if the doctor thinks it is needed) or an echocardiogram.

Long-Term Follow-up Visit:

If you go off treatment (having completed the maximum 24 months on study drug treatment) and have stable disease or response, you will have an MRI scan to check the status of the disease every 2 months for first year after you are off study, then every 3 months for the second year, then every 4 months for the third year, and then every 6 months from then on.

If you continue taking lapatinib after you have completed up to 24 months on study treatment, you will have a clinic visit and an MRI scan to check the status of the disease every 2 months for as long as the doctor thinks it is needed. At the clinic visits, you will be asked how you are doing.

If you went off study treatment because the disease got worse or you experienced intolerable side effects, after the end-of-study visit, the study staff will call you every 3 months from then on to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Temozolomide is Food and Drug Administration (FDA) approved or commercially available for the treatment of tumors of the nervous system. Lapatinib is FDA approved and commercially available for the treatment of breast cancer. However, lapatinib is not FDA approved for the treatment of brain tumors. The use of lapatinib with temozolomide in the treatment of brain tumors and spinal tumors is investigational.

Up to 50 patients will take part in this multicenter study. Up to 30 will be enrolled at MD Anderson.

Inclusion Criteria:

1. 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.
2. History and physical examination, including neurologic examination, within 2 weeks prior to registration.
3. 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.
4. 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.
5. Karnofsky performance status >/= 70
6. Age >/= 18
7. Complete blood count (CBC)/differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows: 1) Absolute neutrophil count (ANC) >/= 1,500/mm^3. 2) Platelets >/= 100,000 cells/mm^3. 3) Hemoglobin >/= 10.0 gm/dL (Note: The use of transfusion or other intervention to achieve Hgb >/= 10.0 is acceptable). 4) White blood cell count (WBC) >/= 3,000/mcL.
8. Adequate liver function within 14 days prior to registration, defined as follows: serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] < 2.5 times the upper limit of normal, Bilirubin </= 1.6 mg/dL
9. Adequate renal function within 14 days prior to registration, defined as follows: Creatinine < 1.7 mg/dL
10. Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of: 1) 28 days from the administration of any investigational agent. 2) 28 days from administration of prior cytotoxic therapy with the following exceptions: (a) 14 days from administration of vincristine. (b) 42 days from administration of nitrosoureas. (c) 21 days from administration of procarbazine.
11. ( 11. continued) 3) 7 days from administration of non-cytotoxic agents [e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)]. 4) 28 days from prior radiation therapy.
12. 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.
13. 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.
14. 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 MD Anderson Cancer Center Office of Multicenter Clinical Research (MDACC OMCR) database prior to treatment with study drug.
15. Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration.
16. Women of childbearing potential and male participants must practice adequate contraception
17. All patients must have an left ventricular ejection fraction (LVEF) measurement of at least 50% by Echo or 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:

1. 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
2. Transmural myocardial infarction or unstable angina within 3 months prior to study registration
3. Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >/= 2 mm using the analysis of an electrocardiography (EKG) performed within 14 days prior to registration
4. New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
5. History of stroke or transient ischemic attack within 3 months prior to registration.
6. Inadequately controlled hypertension (systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg despite antihypertensive medication)
7. History of cerebral vascular accident (CVA) within 3 months prior to registration
8. Serious and inadequately controlled cardiac arrhythmia
9. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
10. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
11. Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with acquired immunodeficiency syndrome (AIDS) from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
12. Pregnant or nursing women because of concern of fetal/infant exposure to these agents
13. 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).
14. Patients cannot be receiving enzyme-inducing anti-epileptic Drugs (EIAEDs) nor any other Image result for CYP3A4 Cytochrome P450 3A4 (CYP3A4) inducers such as rifampin or St. John's wort beginning at least 14 days prior to registration Step 2.
15. Patients cannot be receiving CYP3A4 inhibitors beginning at least 7 days prior to registration Step 2.
16. 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).
17. Patients cannot be receiving HAART (Highly Active Anti-Retroviral Therapy) therapy.

Date treatment consent signed to date off study, approximately 111 months and 26 days.

8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.