Medulloblastoma RecurrentPhase 2MEMMATNCT01356290
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
A Phase 2 study testing Bevacizumab, Thalidomide and Celecoxib in people with Medulloblastoma Recurrent and Ependymoma Recurrent, run by Medical University of Vienna at 22 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 19 years
- Conditions the study is for
- Medulloblastoma Recurrent, Ependymoma Recurrent, ATRT Recurrent
- What is being tested?
- Bevacizumab, Thalidomide and Celecoxib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 232 participants
- Where
- 22 sitesin 8 countries
- Study dates
- Apr 2014to Apr 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
22 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
22 sites in 8 countries
Sweden6 sites, 6 recruiting
- Recruiting
Sahlgrenska Universitetssjukhuset
Gothenburg, 416 85
Karin Fritzson, +46 31 343 58 65, karin.fritzson@vgregion.se
Anna Schröder- Håkansson, +46 31 343 58 65, anna.schroder_hakansson@vgregion.se
- Recruiting
Universitetssjukhuset Linköping
Linköping, 581 85
Birgitta Hellström, +46 10 103 13 54, birgitta.hellstrom@regionostergotland.se
Pernilla Augustsson, +46 10-103 13 50, pernilla.augustsson@regionostergotland.se
- Recruiting
Skånes universitetssjukhus
Lund, 221 85
Yvonne Håkansson, +46 46-17 80 64, Yvonne.Hakansson@skane.se
Simon Johansson, +46 46-17 80 64, simon.johansson@skane.se
- Recruiting
Karolinska University Hospital
Stockholm, SE-171 76
Carina Rinaldo, +46 8 517 701 51, carina.rinaldo@karolinska.se
Yvonne Copeland, +46 8 517 724 84, yvonne.copeland-wahlo@karolinska.se
- Recruiting
Norrlands Universitetssjukhus
Umeå, 901 85
Marita Wikström-Larsson, +46 90-785 02 44, Marita.Vikstrom.Larsson@vll.se
Mattias Mattsson
- Recruiting
Akademiska sjukhuset
Uppsala, 751 85
Katarina Vallin, +46 18 611 34 94, katarina.vallin@akademiska.se
Anders Öberg, MD
Austria5 sites, 5 recruiting
- Recruiting
Medical University of Graz
Graz, 8036
Elisabeth Hulla-Gumbsch, +43 316 385 ext. 82686, elisabeth.hulla-gumbsch@klinikum-graz.at
Martin Benesch, MD
- Recruiting
Medical University of Innsbruck
Innsbruck, 6020
Yvonne Ennemoser, MSc, +43 512 504 ext. 23605, yvonne.ennemoser@tirol-kliniken.at
Roman Crazzolara, MD
- Recruiting
Kepler Universitätsklinikum Med Campus IV
Linz, 4020
Martina Winkler, +43 5 7680 84 ext. 24302, martina.winkler@gespag.at
Barbara Winkler, MD
- Recruiting
Salzburger Universitätsklinikum
Salzburg, 5020
Neil Jones, MD, +43 662 448257 ext. 759, n.jones@salk.at
Neil Jones, MD
- Recruiting
Medical University of Vienna
Vienna, 1090
Andreas Peyrl, MD, +43 1 40400 ext. 32320, andreas.peyrl@meduniwien.ac.at
Johannes Gojo, MD, +43 1 40400 ext. 32320, johannes.gojo@meduniwien.ac.at
United States4 sites, 2 recruiting
- Recruiting
Dell Children's Medical Group SFC-HEM/ONC
Austin, Texas, 78723
Ashley Ratcliffe, 512 628 1900, aeRatcliff@ascension.org
Virginia Harrod, MD
- Terminated
Dana-Farber Cancer Institute and Boston Children's Hospital
Boston, Massachusetts, 02215
- Terminated
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2605
- Recruiting
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 48503
Rebecca Loret de Mola, 616 267 0334, rebecca.loretdemola@helendevoschildrens.org
Rebecca Loret De Mola, MD
Czechia2 sites, 1 recruiting
- Recruiting
University Hospital Brno
Brno, 61300
Alexandra Martincekova, MD, +420532234755, Martincekova.Alexandra@fnbrno.cz
Jaroslav Sterba, MD
- Withdrawn
Motol University Hospital Prague
Prague, 15006
France2 sites, 1 recruiting
- Terminated
Centre Oscar Lambret
Lille, 59037
- Recruiting
Centre Léon Bérard
Lyon, 69373
Pierre Leblond, MD, +33 4 78 78 28 28, pierre.leblond@ihope.fr
Pierre Leblond, MD
Denmark1 site, 1 recruiting
- Recruiting
University hospital Rigshospitalet
Copenhagen, 2100
Karsten Nysom, MD, +45 3545 0809, karsten.nysom@regionh.dk
Karsten Nysom, MD
Norway1 site, 1 recruiting
- Recruiting
Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
Bergen, Bergen, 5021
Ingrid Torsvik, +4705300 ext. +4755975147, ingrid.kristin.torsvik@helse-bergen.no
Ingrid Torsvik, MD
Spain1 site, 1 recruiting
- Recruiting
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
Alvaro Lassaletta, MD, PhD, +34 915 035938 ext. 377, alvaro.lassaletta@salud.madrid.org
Alvaro Lassaletta, MD, PhD
About this study
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
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.
Read more
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.
- Being tested
- Bevacizumab, Thalidomide, Celecoxib, Fenofibric acid, Etoposide
- Keywords
- Medulloblastoma, Ependymoma, ATRT, Relapse, Children, antiangiogenic, metronomic, intraventricular, Rare CNS tumor
- Medical subject headings
- Medulloblastoma, Ependymoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
10mg/kg, intravenous (iv), biweekly, 2 years
ThalidomideDrug
3mg/kg, oral, daily, 2 years
CelecoxibDrug
50-400mg, oral bid, daily, 2 years
Fenofibric acidDrug
90mg/m2, oral, daily, 2 years
EtoposideDrug
35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
CyclophosphamideDrug
2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
EtoposideDrug
0.5mg, intraventricular, day 1-5, every four weeks, alternating with intraventricular cytarabine, 2 years
CytarabineDrug
16-30mg, intraventricular twice weekly for two weeks out of every four weeks, alternating with intraventricular etoposide phosphate, 2 years
Temozolomide (TMZ)Drug
Stratum IV; 150mg/m2, day 1-5 every four weeks, 1 year
IrinotecanDrug
Stratum IV; 50mg/m2, day 1-5 every four weeks, 1 year
| Study group | Role | What they receive |
|---|---|---|
| Standard Arm (Stratum II, III, IV, V) | Other | Etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt Receives: Drug: Bevacizumab; Drug: Thalidomide; Drug: Celecoxib; Drug: Fenofibric acid; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Cytarabine |
| Experimental arm (Stratum IV) | Experimental | Temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt Receives: Drug: Bevacizumab; Drug: Thalidomide; Drug: Celecoxib; Drug: Fenofibric acid; Drug: Etoposide; Drug: Cytarabine; Drug: Temozolomide (TMZ); Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
Measured: 8 years
Secondary outcomes (7)
Overall survival rate
The percentage of patients in the study who are alive for a certain period of time (6, 12, 24, and 36 months) after start of treatment with an antiangiogenic multidrug-regime
Measured: 8 years
Progression free survival rate
The percentage of patients in the study who are alive with a non-progressive disease for a certain period of time (6, 12, 24, and 36 months) after start of treatment with an antiangiogenic multidrug-regime.
Measured: 8 years
Toxicity
To evaluate and document toxicities from chronic administration of these drugs at the doses prescribed in this protocol in patients with recurrent or progressive medulloblastoma. These will be descriptive in nature.
Measured: 8 years
Feasibility
To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
Measured: 6 years
Quality of life
Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
Measured: 8 years
Prognostic factors
To evaluate the influence of tumor biology(histologic subgroups, metastatic stage, age at first diagnosis [<3 years, >3 years]), age at start of antiangiogenic therapy, sex, duration of remission prior to antiangiogenic therapy, number of recurrences.
Measured: 8 years
Angiogenic factors
To evaluate serum markers for in-vitro correlative studies of tumor response.
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2011 (estimated)
- Study startApr 2014
- Primary completionApr 2030 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Medulloblastoma RecurrentStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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;
- Masking
- None (open label)
- Enrolment
- 232 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andreas Peyrl, Medical University of Vienna
- Investigators
- Andreas Peyrl, MD, Principal investigator, Medical University of ViennaAmedeo A Azizi, MD, Study director, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01356290
- Sponsor's protocol ID
- MUV-MEMMAT-01
- Acronym
- MEMMAT
- Status last verified
- Oct 2026
- First submitted
- 17 May 2011
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37883081Slavc 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.
PubMed 36291912