ANGIOCOMB Antiangiogenic Therapy for Pediatric Patients With Diffuse Brain Stem and Thalamic Tumors

All pediatric patients (aged 1-16 yrs) with newly diagnosed diffuse brain stem tumor or inoperable thalamic tumor which infiltrate brain stem from the pediatric oncology units in Denmark, Finland, Iceland, Norway and Sweden will be eligible. A possible tumor biopsy with histologic findings is not taken into account. The diagnosis is based on MRI. The patients are given a conventional local radiotherapy of 54 Gy, during which the patient also receives topotecan as radiosensitizer. Within four weeks after completed radiotherapy, the investigational drugs are started. If the family for some reason refuses radiotherapy, the investigational therapy may still be considered. The guardians and age-appropriate patients are asked for written informed consent. If the family is not willing to participate in the trial, the patient is treated according to the currently best available therapy (meaning RT without topotecan as palliative therapy). The family has the right to withdraw from the study, whenever they so wish.

Brain MRI at initial diagnosis, before the start of triple medication, and q 3 mo after initiation of triple medication, if not otherwise clinically indicated. In case it is decided to continue medication with progression in MRI, repeat MRIs are recommended every month. MRI should also be registered, if feasible, at the discontinuation of the medication.

The clinical follow-up, as well as MRI follow-up, on clinical indications will continue also after discontinuation of therapy.

PET-CT and/or MRI spectroscopy should be considered at diagnosis and at 3 mo after the start of triple medication.