Antiangiogenic Therapy for Children with Recurrent Medulloblastoma, Ependymoma and ATRT

Inclusion Criteria:

• Relapsed or progressive medulloblastoma, ependymoma or ATRT (at least one site ofuntreated recurrent disease)

• Histological confirmation of medulloblastoma, ependymoma or ATRT at diagnosis orrelapse

• Female or male, aged from 0 to <20 years (at time of original diagnosis)

• Participants must have normal organ and bone marrow function (ALT <5x institutionalupper limit of normal, creatinine <1.5x institutional upper limit of normal for age,WBC >1000/mm3, platelets > 20,000/mm3. Patients with values less than WBC 2000/mm3or platelets 50,000/mm3 will require initiation of treatment with etoposide andcyclophosphamide at a lower starting dose as defined within the protocol.

• Karnofsky performance status ≥50. For infants and children less than 12 years ofage, the Lansky play scale ≥50% will be used

• Written informed consent of patients and / or parents

Exclusion Criteria:

• Active infection

• VP-shunt dependency

• Pregnancy or breast feeding

• Conventional chemotherapy, antiangiogenic treatment or complete irradiation of alldisease for current relapse (surgery may be performed before antiangiogenictreatment; patients with sites of disease not irradiated are still eligible for theprotocol)

• Known hypersensitivity to any of the drugs in the protocol

• Active peptic ulcer

• Any significant cardiovascular disease not controled by standard therapy e.g.systemic hypertension

• Anticipation of the need for major elective surgery during the course of the studytreatment

• Any disease or condition that contraindicates the use of the studymedication/treatment or places the patient at an unacceptable risk of experiencingtreatment-related complications

• Non-healing surgical wound

• A bone fracture that has not satisfactorily healed