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NCT01356290PHASE2Recruiting

Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors

Medical University of Vienna

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

Inclusion criteria for patients Stratum I: Relapsed or progressive medulloblastoma - completed Stratum II: Relapsed or progressive ependymoma (at least one site of untreated recurrent disease) Stratum III: Relapsed or progressive ATRT (at least one site of untreated recurrent disease) Stratum IV: Relapsed or progressive medulloblastoma (at least one site of untreated recurrent disease) Stratum V: Relapsed or progressive CNS tumor of various histologies or patients with exclusion criteria or adult patients (explorative) Histological confirmation at diagnosis or relapse Stratum IV: Confirmation of the medulloblastoma group by methylation; IDAT (Intensity Data; raw data of methylation array) 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 institutional upper 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/mm3 or platelets 50,000/mm3 will require initiation of treatment with etoposide and cyclophosphamide at a lower starting dose as defined within the protocol Karnofsky performance status ≥50. For infants and children less than 12 years of age, the Lansky play scale ≥50% will be used Written informed consent of patients and / or legal guardian Exclusion criteria for patients VP- or subdural peritoneal shunt dependency (can be included in Stratum V) Prior treatment with temozolomide/irinotecan (can be included in Stratum V) Active infection, pregnancy or breast feeding Treatment for current relapse (surgery may be performed before MEMMAT treatment; patients with sites of disease not irradiated are still eligible for the protocol) Known hypersensitivity to any of the drugs in the protocol Active peptic ulcer Any significant cardiovascular disease not controlled by standard therapy e.g. systemic hypertension Anticipation of the need for major elective surgery during the course of the study treatment Any disease or condition that contraindicates the use of the study medication/treatment or places the patient at an unacceptable risk of experiencing treatment-related complications Non-healing surgical wound A bone fracture that has not satisfactorily healed

Interventions

DRUG

Bevacizumab

DRUG

Thalidomide

DRUG

Celecoxib

DRUG

Fenofibric acid

DRUG

Etoposide

DRUG

Cyclophosphamide

DRUG

Etoposide phosphate

DRUG

Cytarabine

DRUG

Temozolomide (TMZ)

DRUG

Irinotecan

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Conditions

Medulloblastoma RecurrentEpendymoma RecurrentATRT RecurrentRare CNS Tumor Recurrent

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