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

NCT01356290 | Recruiting Phase 2 DMC

• 1 other identifier: MUV-MEMMAT-01
• Study Type: interventional
• Target: 232
• Locations: 8 countries
• Sites: 22

Brief 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.

Conditions

Medulloblastoma Recurrent; Ependymoma Recurrent; ATRT Recurrent; Rare CNS Tumor Recurrent

Keywords

Medulloblastoma; Ependymoma; ATRT; Relapse; Children; antiangiogenic; metronomic; intraventricular; Rare CNS tumor

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Response rate (Complete remission, partial response, stable disease =\[CR+PR+SD\]/n) 6 months after start of antiangiogenic treatment

  8 years

Secondary Outcomes (7)

• Overall survival rate

  8 years

• Progression free survival rate

  8 years

• Toxicity

  8 years

• Feasibility

  6 years

• Quality of life

  8 years

Study Arms (2)

Standard Arm (Stratum II, III, IV, V)

OTHER

Etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt

Drug: Bevacizumab; Drug: Thalidomide; Drug: Celecoxib; Drug: Fenofibric acid; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Etoposide phosphate; Drug: Cytarabine

Experimental arm (Stratum IV)

EXPERIMENTAL

Temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt

Drug: Bevacizumab; Drug: Thalidomide; Drug: Celecoxib; Drug: Fenofibric acid; Drug: Etoposide phosphate; Drug: Cytarabine; Drug: Temozolomide (TMZ); Drug: Irinotecan

Interventions

Bevacizumab DRUG

10mg/kg, intravenous (iv), biweekly, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Thalidomide DRUG

3mg/kg, oral, daily, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Celecoxib DRUG

50-400mg, oral bid, daily, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Fenofibric acid DRUG

90mg/m2, oral, daily, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Etoposide DRUG

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

Standard Arm (Stratum II, III, IV, V)

Etoposide phosphate DRUG

0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Cytarabine DRUG

16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year

Experimental arm (Stratum IV); Standard Arm (Stratum II, III, IV, V)

Temozolomide (TMZ) DRUG

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

Experimental arm (Stratum IV)

Irinotecan DRUG

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

Experimental arm (Stratum IV)

Cyclophosphamide DRUG

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

Standard Arm (Stratum II, III, IV, V)

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (22)

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

Chicago, Illinois, 60611-2605, United States

TERMINATED

Dana-Farber Cancer Institute and Boston Children's Hospital

Boston, Massachusetts, 02215, United States

TERMINATED

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 48503, United States

RECRUITING

Dell Children's Medical Group SFC-HEM/ONC

Austin, Texas, 78723, United States

RECRUITING

Medical University of Graz

Graz, 8036, Austria

RECRUITING

Medical University of Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Kepler Universitätsklinikum Med Campus IV

Linz, 4020, Austria

RECRUITING

Salzburger Universitätsklinikum

Salzburg, 5020, Austria

RECRUITING

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

University Hospital Brno

Brno, 61300, Czechia

RECRUITING

Motol University Hospital Prague

Prague, 15006, Czechia

RECRUITING

University hospital Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Centre Oscar Lambret

Lille, 59037, France

TERMINATED

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus

Bergen, 5021, Norway

RECRUITING

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, 416 85, Sweden

RECRUITING

Universitetssjukhuset Linköping

Linköping, 581 85, Sweden

RECRUITING

Skånes universitetssjukhus

Lund, 221 85, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, SE-171 76, Sweden

RECRUITING

Norrlands Universitetssjukhus

Umeå, 901 85, Sweden

RECRUITING

Akademiska sjukhuset

Uppsala, 751 85, Sweden

RECRUITING

Related Publications (2)

• Peyrl A, Chocholous M, Sabel M, Lassaletta A, Sterba J, Leblond P, Nysom K, Torsvik I, Chi SN, Perwein T, Jones N, Holm S, Nyman P, Morse H, Oberg A, Weiler-Wichtl L, Leiss U, Haberler C, Schmook MT, Mayr L, Dieckmann K, Kool M, Gojo J, Azizi AA, Andre N, Kieran M, Slavc I. Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial. JAMA Oncol. 2023 Dec 1;9(12):1688-1695. doi: 10.1001/jamaoncol.2023.4437.

  PMID: 37883081 DERIVED

• Slavc I, Mayr L, Stepien N, Gojo J, Aliotti Lippolis M, Azizi AA, Chocholous M, Baumgartner A, Hedrich CS, Holm S, Sehested A, Leblond P, Dieckmann K, Haberler C, Czech T, Kool M, Peyrl A. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach. Cancers (Basel). 2022 Oct 19;14(20):5128. doi: 10.3390/cancers14205128.

  PMID: 36291912 DERIVED

MeSH Terms

Conditions

Medulloblastoma; Ependymoma; Recurrence

Interventions

Bevacizumab; Thalidomide; Celecoxib; fenofibric acid; Etoposide; Cyclophosphamide; etoposide phosphate; Cytarabine; Temozolomide; Irinotecan

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Imidazoles; Camptothecin; Alkaloids

Study Officials

• Andreas Peyrl, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Peyrl, MD

CONTACT

+43 1 40400; andreas.peyrl@meduniwien.ac.at

Amedeo A Azizi, MD

CONTACT

+43 1 40400; amedeo.azizi@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: 5 Strata: Stratum I: medulloblastoma - 40 patients -completed (see Peyrl et al, 2023, JAMA Oncology); Stratum II: ependymoma - 30 patients; Stratum III: ATRT - 30 patients); Stratum IV: medulloblastoma - randomized, 132 patients; Stratum V: Rare CNS tumors and patients with exclusion criteria - exploratory;

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: May 19, 2011
• Study Start: April 1, 2014
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

AU (5); CZ (2); ES (1); FR (2); DK (1); SE (6); NO (1); US (4)