search
Back to results

Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT (MEMMAT)

Primary Purpose

Medulloblastoma Recurrent, Ependymoma Recurrent, ATRT Recurrent

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bevacizumab
Thalidomide
Celecoxib
Fenofibric acid
Etoposide
Cyclophosphamide
Etoposide phosphate
Cytarabine
Sponsored by
Medical University of Vienna
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medulloblastoma Recurrent focused on measuring Medulloblastoma, Ependymoma, ATRT, Relapse, Children, antiangiogenic, metronomic, intraventricular

Eligibility Criteria

undefined - 19 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Relapsed or progressive medulloblastoma, ependymoma or ATRT (at least one site of untreated recurrent disease)
  • Histological confirmation of medulloblastoma, ependymoma or ATRT at diagnosis or relapse
  • 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 parents

Exclusion Criteria:

  • Active infection
  • VP-shunt dependency
  • Pregnancy or breast feeding
  • Conventional chemotherapy, antiangiogenic treatment or complete irradiation of all disease for current relapse (surgery may be performed before antiangiogenic 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 controled 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

Sites / Locations

  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Dana-Farber Cancer Institute and Boston Children's Hospital
  • Helen DeVos Children's HospitalRecruiting
  • Dell Children's Medical Group SFC-HEM/ONCRecruiting
  • Medical University of GrazRecruiting
  • Medical University of InnsbruckRecruiting
  • Kepler Universitätsklinikum Med Campus IVRecruiting
  • Salzburger UniversitätsklinikumRecruiting
  • Medical University of ViennaRecruiting
  • University Hospital BrnoRecruiting
  • Motol University Hospital PragueRecruiting
  • University hospital RigshospitaletRecruiting
  • Centre Oscar Lambret
  • Centre Léon BérardRecruiting
  • Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehusRecruiting
  • Hospital Infantil Universitario Nino JesusRecruiting
  • Sahlgrenska UniversitetssjukhusetRecruiting
  • Universitetssjukhuset LinköpingRecruiting
  • Skånes universitetssjukhusRecruiting
  • Karolinska University HospitalRecruiting
  • Norrlands UniversitetssjukhusRecruiting
  • Akademiska sjukhusetRecruiting

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.
Feasibility
To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
Quality of life
Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
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.
Angiogenic factors
To evaluate serum markers for in-vitro correlative studies of tumor response.

Full Information

First Posted
May 17, 2011
Last Updated
April 19, 2023
Sponsor
Medical University of Vienna
search

1. Study Identification

Unique Protocol Identification Number
NCT01356290
Brief Title
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT
Acronym
MEMMAT
Official Title
A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma and ATRT
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2014 (Actual)
Primary Completion Date
April 2026 (Anticipated)
Study Completion Date
April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients with relapsed medulloblastoma, ependymoma and ATRT have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. Antiangiogenetic therapy has emerged as new treatment option in solid malignancies. The frequent, metronomic schedule targets both proliferating tumor cells and endothelial cells, and minimizes toxicity. In this study the investigators will evaluate the use of biweekly intravenous bevacizumab in combination with five oral drugs (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma and ATRT, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. The primary objective of the MEMMAT trial is to evaluate the activity of this multidrug antiangiogenic approach in these heavily pretreated children and young adults. Additionally, progression-free survival (PFS), overall survival (OS), as well as feasibility and toxicity will be examined.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medulloblastoma Recurrent, Ependymoma Recurrent, ATRT Recurrent
Keywords
Medulloblastoma, Ependymoma, ATRT, Relapse, Children, antiangiogenic, metronomic, intraventricular

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
3 Strata (medulloblastoma - 40 patients; ependymoma - 30 patients; ATRT - 30 patients)
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
10mg/kg, intravenous (iv), biweekly, 1 year
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Intervention Description
3mg/kg, oral, daily, 1 year
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Intervention Description
50-400mg, oral bid, daily, 1 year
Intervention Type
Drug
Intervention Name(s)
Fenofibric acid
Intervention Description
90mg/m2, oral, daily, 1 year
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
Intervention Type
Drug
Intervention Name(s)
Etoposide phosphate
Intervention Description
0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year
Primary Outcome Measure Information:
Title
Efficacy
Description
Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
Time Frame
8 years
Secondary Outcome Measure Information:
Title
Overall survival rate
Description
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
Time Frame
8 years
Title
Progression free survival rate
Description
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.
Time Frame
8 years
Title
Toxicity
Description
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.
Time Frame
8 years
Title
Feasibility
Description
To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
Time Frame
6 years
Title
Quality of life
Description
Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
Time Frame
8 years
Title
Prognostic factors
Description
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.
Time Frame
8 years
Title
Angiogenic factors
Description
To evaluate serum markers for in-vitro correlative studies of tumor response.
Time Frame
8 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed or progressive medulloblastoma, ependymoma or ATRT (at least one site of untreated recurrent disease) Histological confirmation of medulloblastoma, ependymoma or ATRT at diagnosis or relapse 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 parents Exclusion Criteria: Active infection VP-shunt dependency Pregnancy or breast feeding Conventional chemotherapy, antiangiogenic treatment or complete irradiation of all disease for current relapse (surgery may be performed before antiangiogenic 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 controled 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreas Peyrl, MD
Phone
+43 1 40400
Ext
32320
Email
andreas.peyrl@meduniwien.ac.at
First Name & Middle Initial & Last Name or Official Title & Degree
Irene Slavc, MD
Phone
+43 1 40400
Ext
32320
Email
irene.slavc@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Peyrl, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Monika Chocholous, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Study Chair
Facility Information:
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Individual Site Status
Terminated
Facility Name
Dana-Farber Cancer Institute and Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Terminated
Facility Name
Helen DeVos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Loret de Mola
Phone
616-267-0334
Email
rebecca.loretdemola@helendevoschildrens.org
First Name & Middle Initial & Last Name & Degree
Rebecca Loret De Mola, MD
Facility Name
Dell Children's Medical Group SFC-HEM/ONC
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Ratcliffe
Phone
512-628-1900
Email
aeRatcliff@ascension.org
First Name & Middle Initial & Last Name & Degree
Virginia Harrod, MD
Facility Name
Medical University of Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabeth Hulla-Gumbsch
Phone
+43 316 385
Ext
82686
Email
elisabeth.hulla-gumbsch@klinikum-graz.at
First Name & Middle Initial & Last Name & Degree
Martin Benesch, MD
Facility Name
Medical University of Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvonne Ennemoser, MSc
Phone
+43 512 504
Ext
23605
Email
yvonne.ennemoser@tirol-kliniken.at
First Name & Middle Initial & Last Name & Degree
Roman Crazzolara, MD
Facility Name
Kepler Universitätsklinikum Med Campus IV
City
Linz
ZIP/Postal Code
4020
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martina Winkler
Phone
+43 5 7680 84
Ext
24302
Email
martina.winkler@gespag.at
First Name & Middle Initial & Last Name & Degree
Georg Ebetsberger, MD
Facility Name
Salzburger Universitätsklinikum
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neil Jones, MD
Phone
+43 662 448257
Ext
759
Email
n.jones@salk.at
First Name & Middle Initial & Last Name & Degree
Agnes Gamper, MD
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Peyrl, MD
Phone
+43 1 40400
Ext
32320
Email
andreas.peyrl@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Irene Slavc, MD
Phone
+43 1 40400
Ext
32320
Email
irene.slavc@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Andreas Peyrl, MD
First Name & Middle Initial & Last Name & Degree
Irene Slavc, MD
Facility Name
University Hospital Brno
City
Brno
ZIP/Postal Code
61300
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Martincekova, MD
Phone
+420532234755
Email
Martincekova.Alexandra@fnbrno.cz
First Name & Middle Initial & Last Name & Degree
Jaroslav Sterba, MD
First Name & Middle Initial & Last Name & Degree
Zdenek Pavelka, MD
Facility Name
Motol University Hospital Prague
City
Prague
ZIP/Postal Code
15006
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Klara Hruba
Phone
+42 0224436401
Email
klara.hruba@fnmotol.cz
First Name & Middle Initial & Last Name & Degree
David Sumerauer, MD
Facility Name
University hospital Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karsten Nysom, MD
Phone
+45 3545 0809
Email
karsten.nysom@regionh.dk
First Name & Middle Initial & Last Name & Degree
Karsten Nysom, MD
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Terminated
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69373
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Leblond, MD
Phone
+33 4 78 78 28 28
Email
pierre.leblond@ihope.fr
First Name & Middle Initial & Last Name & Degree
Pierre Leblond, MD
Facility Name
Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingrid Torsvik
Phone
+4705300
Ext
+4755975147
Email
ingrid.kristin.torsvik@helse-bergen.no
First Name & Middle Initial & Last Name & Degree
Ingrid Torsvik, MD
Facility Name
Hospital Infantil Universitario Nino Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alvaro Lassaletta, MD, PhD
Phone
+34 915 035938
Ext
377
Email
alvaro.lassaletta@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Alvaro Lassaletta, MD, PhD
Facility Name
Sahlgrenska Universitetssjukhuset
City
Göteborg
ZIP/Postal Code
416 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karin Fritzson
Phone
+46 31 343 58 65
Email
karin.fritzson@vgregion.se
First Name & Middle Initial & Last Name & Degree
Anna Schröder- Håkansson
Phone
+46 31 343 58 65
Email
anna.schroder_hakansson@vgregion.se
First Name & Middle Initial & Last Name & Degree
Magnus Sabel, MD
First Name & Middle Initial & Last Name & Degree
Birgitta Lannering, Prof
Facility Name
Universitetssjukhuset Linköping
City
Linköping
ZIP/Postal Code
581 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birgitta Hellström
Phone
+46 10 103 13 54
Email
birgitta.hellstrom@regionostergotland.se
First Name & Middle Initial & Last Name & Degree
Pernilla Augustsson
Phone
+46 10-103 13 50
Email
pernilla.augustsson@regionostergotland.se
First Name & Middle Initial & Last Name & Degree
Irene Devenney, MD
Facility Name
Skånes universitetssjukhus
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvonne Håkansson
Phone
+46 46-17 80 64
Email
Yvonne.Hakansson@skane.se
First Name & Middle Initial & Last Name & Degree
Simon Johansson
Phone
+46 46-17 80 64
Email
simon.johansson@skane.se
First Name & Middle Initial & Last Name & Degree
Helena Mörse, MD
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carina Rinaldo
Phone
+46 8 517 701 51
Email
carina.rinaldo@karolinska.se
First Name & Middle Initial & Last Name & Degree
Yvonne Copeland
Phone
+46 8 517 724 84
Email
yvonne.copeland-wahlo@karolinska.se
First Name & Middle Initial & Last Name & Degree
Stefan Holm, MD
Facility Name
Norrlands Universitetssjukhus
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marita Wikström-Larsson
Phone
+46 90-785 02 44
Email
Marita.Vikstrom.Larsson@vll.se
First Name & Middle Initial & Last Name & Degree
Mattias Mattsson
Facility Name
Akademiska sjukhuset
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katarina Vallin
Phone
+46 18 611 34 94
Email
katarina.vallin@akademiska.se
First Name & Middle Initial & Last Name & Degree
Anders Öberg, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
36291912
Citation
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.
Results Reference
derived

Learn more about this trial

Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT

We'll reach out to this number within 24 hrs