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RECRUITING

NCT01356290

PHASE2

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

Sponsor: Medical University of Vienna

View on ClinicalTrials.gov

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.

Official title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors

Key Details

Gender

All

Age Range

Any - 19 Years

Study Type

INTERVENTIONAL

Enrollment

232

Start Date

2014-04

Completion Date

2030-04

Last Updated

2026-09-10

Healthy Volunteers

Conditions

Medulloblastoma Recurrent Ependymoma Recurrent ATRT Recurrent Rare CNS Tumor Recurrent

Interventions

DRUG

Bevacizumab

10mg/kg, intravenous (iv), biweekly, 2 years

DRUG

Thalidomide

3mg/kg, oral, daily, 2 years

DRUG

Celecoxib

50-400mg, oral bid, daily, 2 years

DRUG

Fenofibric acid

90mg/m2, oral, daily, 2 years

DRUG

Etoposide

35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

DRUG

Cyclophosphamide

2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

DRUG

Etoposide

0.5mg, intraventricular, day 1-5, every four weeks, alternating with intraventricular cytarabine, 2 years

DRUG

Cytarabine

16-30mg, intraventricular twice weekly for two weeks out of every four weeks, alternating with intraventricular etoposide phosphate, 2 years

DRUG

Temozolomide (TMZ)

Stratum IV; 150mg/m2, day 1-5 every four weeks, 1 year

DRUG

Irinotecan

Stratum IV; 50mg/m2, day 1-5 every four weeks, 1 year

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

Locations (22)

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Dana-Farber Cancer Institute and Boston Children's Hospital

Boston, Massachusetts, United States

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Dell Children's Medical Group SFC-HEM/ONC

Austin, Texas, United States

Medical University of Graz

Graz, Austria

Medical University of Innsbruck

Innsbruck, Austria

Kepler Universitätsklinikum Med Campus IV

Linz, Austria

Salzburger Universitätsklinikum

Salzburg, Austria

Medical University of Vienna

Vienna, Austria

University Hospital Brno

Brno, Czechia

Motol University Hospital Prague

Prague, Czechia

University hospital Rigshospitalet

Copenhagen, Denmark

Centre Oscar Lambret

Lille, France

Centre Léon Bérard

Lyon, France

Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus

Bergen, Bergen, Norway

Hospital Infantil Universitario Nino Jesus

Madrid, Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden

Universitetssjukhuset Linköping

Linköping, Sweden

Skånes universitetssjukhus

Lund, Sweden

Karolinska University Hospital

Stockholm, Sweden

Norrlands Universitetssjukhus

Umeå, Sweden

Akademiska sjukhuset

Uppsala, Sweden

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (22)