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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether initial local irradiation with topotecan and following oral antiangiogenic drugs, thalidomide, celecoxib and etoposide are effective in the treatment of pediatric diffuse brainstem tumor.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Brainstem Glioma

Intervention / Treatment
-----------------
* Drug: Thalidomide, etoposide, celecoxib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -pediatric diffuse brainstem tumor Exclusion Criteria: wish of the family need for strong painrelievers decreased level of consciousness inability to swallow.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide, etoposide, celecoxib<br>Single arm study,phase II | Drug: Thalidomide, etoposide, celecoxib<br>* Thalidomide p.o. 1 mg/kg/day/1; the dose is gradually escalated, the maximum dose being 6 mg/kg/day. (The individual dose is set based on adverse effects.) Celecoxib p.o. 230 mg/m2/day/1-2, or in small children at 7 mg/kg/day in 1-2 doses. Etoposide p.o. the initial dosage 20 mg/m2/day; the dose is gradually escalated, the maxi 70 mg/m2/day.<br>* Other names: celebra (celecoxib);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Primary outcome measure is survival in months. | up to five years |