Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

Inclusion Criteria

• Age: Patient must be 16 years of age) or Lansky Performance Score (LPS for or = 50 assessed within 2 weeks prior to registration.
• Evidence of recovery from any prior chemotherapy. No myelosuppressive anticancer chemotherapy or biological therapy within 3 weeks (6 weeks if a nitrosourea or mitomycin C agent) prior to registration.
• Prior/Concurrent Therapy: external beam radiation therapy (XRT): Patients must have had prior radiation therapy for treatment of their ependymoma. XRT must be > or = 3 months prior to registration for craniospinal irradiation (> or = 18 Gy); > or = 4 weeks for local radiation to primary tumor; and > or = 2 weeks prior to registration for focal irradiation to symptomatic metastatic sites.
• Prior/Concurrent Therapy: Bone Marrow Transplant: > or = 3 months prior to registration for autologous bone marrow/stem cell transplant.
• Prior/Concurrent Therapy: Anti-convulsants: Patients with seizure disorder may be enrolled if well controlled. Patients receiving enzyme-inducing anticonvulsants are not eligible for this study. Patients must be off EIACD for at least 2 weeks prior to registration.
• Prior/Concurrent Therapy: Corticosteroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to registration.
• Prior/Concurrent Therapy: Growth Factors: Off all colony forming growth factor(s) > or = 2 weeks prior to registration (G-CSF, GM-CSF, Erythropoietin).
• Patients must not have received: cytochrome P450 3A4 (CYP3A4) inhibitors within seven (7) days prior to registration on protocol and for the duration of the study. However, amiodarone, another CYP3A4 inhibitor, should have been discontinued 6 months prior to registration and for the duration of the study.
• Patient must not have received: CYP3A4 inducers within fourteen (14) days prior to registration and for the duration of the study.
• Patient must not have received: Cimetidine within 48 hours prior and for the duration of the study.
• The following laboratory values must be assessed within 7 days prior to registration and must be repeated if initial labs were done greater than (>seven) (7) calendar days prior to the start of therapy. Organ Function: Must have adequate organ function and marrow function as defined by the following parameters: Bone Marrow: Absolute neutrophil count >or =1000microliter, Platelets > or = 100,000 microliter (transfusion independent), Hemoglobin >or =8.0 g/dL. Renal: Serum creatinine or = 70ml/min/1.73m2 Hepatic: Total bilirubin or = 2g/dL. No overt renal, hepatic, cardiac or pulmonary disease.
• No overt renal, hepatic, cardiac or pulmonary disease.
• Adequate cardiac function, assessed within 2 weeks prior to registration, defined as: shortening fraction of > or = 27% by echocardiogram, or ejection fracture (LVEF) > or = 50% by gated radionucleotide study.
• Adequate pulmonary function, assessed within 2 weeks prior to registration, defined as: no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
• Signed informed consent according to institutional guidelines must be obtained.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately and will be removed from the study.
• Patient must begin therapy within 7 calendar days of registration.

Exclusion Criteria

• Patients may not have previously been treated with Bevacizumab or Lapatinib.
• Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this the