Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
Start Date
4/1/2014
Completion Date
4/1/2030
Summary
Patients with with recurrent or progressive medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor (ATRT), and CNS tumors of various histologies have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. Antiangiogenesis therapy has emerged as a new treatment option in solid malignancies. The frequent delivery of low doses of chemotherapy, referred to as metronomic or antiangiogenic chemotherapy, targets endothelial cells while reducing the toxicity associated with standard dose chemotherapy. The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma, ATRT, and CNS tumors of various histologies, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. The study will be conducted in independent strata. Stratum I (recurrent medulloblastoma): recently completed (Peyrl, 2023). Stratum II (recurrent ependymoma), III (recurrent ATRT) and V (recurrent CNS tumors of various histologies, patients with exclusion criteria and adult patients): The primary objective is to determine the response rate defined as the percentage of patients with complete response (CR), partial response (PR), stable disease (SD) or lack of recurrence at 6 months after start of antiangiogenic treatment. Stratum IV (recurrent medulloblastoma): To determine whether temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt can increase the response rate after 6 months of treatment, compared with etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt. Additionally, PFS, OS, toxicity, QoL, performance status, predictive and prognostic markers will be examined. In stratum II and III, the study will follow an open label, single arm phase 2 design, and an open label randomized two-arm phase 2 design in Stratum IV, and the exploratory Stratum V.
Eligibility Criteria
Age Range: No minimum to 19 years
Interventions
Bevacizumab
Thalidomide
Celecoxib
Fenofibric acid
Etoposide
Cyclophosphamide
Etoposide phosphate
Cytarabine
Temozolomide (TMZ)
Irinotecan
Conditions
Locations
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois 60611-2605
United States
Dana-Farber Cancer Institute and Boston Children's Hospital
Boston, Massachusetts 02215
United States
Helen DeVos Children's Hospital
Grand Rapids, Michigan 48503
United States
Dell Children's Medical Group SFC-HEM/ONC
Austin, Texas 78723
United States
Medical University of Graz
Graz, 8036
Austria
Medical University of Innsbruck
Innsbruck, 6020
Austria
Kepler Universitätsklinikum Med Campus IV
Linz, 4020
Austria
Salzburger Universitätsklinikum
Salzburg, 5020
Austria
Medical University of Vienna
Vienna, 1090
Austria
University Hospital Brno
Brno, 61300
Czechia
Motol University Hospital Prague
Prague, 15006
Czechia
University hospital Rigshospitalet
Copenhagen, 2100
Denmark
Centre Oscar Lambret
Lille, 59037
France
Centre Léon Bérard
Lyon, 69373
France
Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
Bergen, 5021
Norway
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
Spain
Sahlgrenska Universitetssjukhuset
Gothenburg, 416 85
Sweden
Universitetssjukhuset Linköping
Linköping, 581 85
Sweden
Skånes universitetssjukhus
Lund, 221 85
Sweden
Karolinska University Hospital
Stockholm, SE-171 76
Sweden
Norrlands Universitetssjukhus
Umeå, 901 85
Sweden
Akademiska sjukhuset
Uppsala, 751 85
Sweden