A Phase II Study of Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma
The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.
Stanford is not currently accepting new patients for this trial. You may want to check clinicaltrials.gov to see if other locations are recruiting.
- drug : Lapatinib
- drug : Bevacizumab
Phase: Phase 2
Ages Eligible For Study:
1. Age: Patient must be < or = 21 years of age. 2. Tumor: Patients must have recurrent or refractory intracranial ependymoma (including myxopapillary, clear cell, papillary, tanycytic, and anaplastic ependymoma) or subependymoma. Patients with primary diagnosis of intracranial ependymoma with spinal cord metastases or relapse are eligible. The diagnosis must be confirmed by the CERN enrolling site's pathologist on tissue from either the initial presentation or time of recurrence prior to registration. For central pathology review and trial biological studies, submission of a paraffin block with tumor measuring at least 1 cm x 1 cm in area is preferred, but 15 x 5micro m unstained sections on slides may be provided by the referring laboratory instead. Tissue must be submitted within 60 days after enrollment for central processing and analysis. 3. Patients must have measureable disease which is defined as at least one measurable lesion that can be accurately measured in 2 planes. Diffuse leptomeningeal involvement ("sugar coating") that does not allow measurement of at least one lesion in 2 planes will not be considered measurable disease. 4. Patients may have had any number of prior treatment regimens (including biologic) before or after radiotherapy. Patients may not have previously been treated with Bevacizumab or Lapatinib. Gliadel wafers must be approved by CERN PI (Project Leader, Co-Leader and Protocol PI). 5. Neurological Deficits: Patients with neurological deficits should have deficits that are stable or improving for a minimum of 1 week prior to registration. 6. Performance Score: Karnofsky Performance Scale (KPS for > 16 years of age) or Lansky Performance Score (LPS for < or = 16 years of age) > or = 50 assessed within 2 weeks prior to registration. 7. 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. 8. 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. 9. Prior/Concurrent Therapy: Bone Marrow Transplant: > or = 3 months prior to registration for autologous bone marrow/stem cell transplant. 10. 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. 11. 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. 12. Prior/Concurrent Therapy: Growth Factors: Off all colony forming growth factor(s) > or = 2 weeks prior to registration (G-CSF, GM-CSF, Erythropoietin). 13. 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. 14. Patient must not have received: CYP3A4 inducers within fourteen (14) days prior to registration and for the duration of the study. 15. Patient must not have received: Cimetidine within 48 hours prior and for the duration of the study. 16. 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 = 1.5 times upper limit of institutional for age or glomerular filtration rate (GFR)>or = 70ml/min/1.73m2 Hepatic: Total bilirubin < or = 1.5 times upper limit of normal for age: serum glutamate pyruvate transaminase (SGPT) (ALT)<2.5x institutional upper limit of normal for age and albumin > or = 2g/dL. No overt renal, hepatic, cardiac or pulmonary disease. 17. No overt renal, hepatic, cardiac or pulmonary disease. 18. 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. 19. 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. 20. Signed informed consent according to institutional guidelines must be obtained. 21. 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. 22. Patient must begin therapy within 7 calendar days of registration.