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

January 27, 2024 updated by: Andreas Peyrl, Medical University of Vienna

A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma and ATRT

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Graz, Austria, 8036
      • Innsbruck, Austria, 6020
        • Recruiting
        • Medical University of Innsbruck
        • Contact:
        • Principal Investigator:
          • Roman Crazzolara, MD
      • Linz, Austria, 4020
        • Recruiting
        • Kepler Universitätsklinikum Med Campus IV
        • Contact:
        • Principal Investigator:
          • Georg Ebetsberger, MD
      • Salzburg, Austria, 5020
        • Recruiting
        • Salzburger Universitatsklinikum
        • Principal Investigator:
          • Agnes Gamper, MD
        • Contact:
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andreas Peyrl, MD
        • Sub-Investigator:
          • Irene Slavc, MD
  • Czechia
      • Brno, Czechia, 61300
        • Recruiting
        • University Hospital Brno
        • Contact:
        • Principal Investigator:
          • Jaroslav Sterba, MD
        • Sub-Investigator:
          • Zdenek Pavelka, MD
      • Prague, Czechia, 15006
        • Recruiting
        • Motol University Hospital Prague
        • Contact:
        • Principal Investigator:
          • David Sumerauer, MD
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • University Hospital Rigshospitalet
        • Contact:
        • Principal Investigator:
          • Karsten Nysom, MD
  • France
      • Lille, France, 59037
        • Terminated
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Recruiting
        • Centre Leon Berard
        • Contact:
        • Principal Investigator:
          • Pierre LEBLOND, MD
  • Norway
      • Bergen, Norway, 5021
        • Recruiting
        • Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
        • Contact:
        • Principal Investigator:
          • Ingrid Torsvik, MD
  • Spain
      • Madrid, Spain, 28009
        • Recruiting
        • Hospital Infantil Universitario Nino Jesus
        • Contact:
        • Principal Investigator:
          • Alvaro Lassaletta, MD, PhD
  • Sweden
      • Göteborg, Sweden, 416 85
        • Recruiting
        • Sahlgrenska Universitetssjukhuset
        • Contact:
        • Contact:
        • Principal Investigator:
          • Magnus Sabel, MD
        • Sub-Investigator:
          • Birgitta Lannering, Prof
      • Linköping, Sweden, 581 85
      • Lund, Sweden, 221 85
        • Recruiting
        • Skanes universitetssjukhus
        • Contact:
        • Contact:
        • Principal Investigator:
          • Helena Mörse, MD
      • Stockholm, Sweden, SE-171 76
      • Umeå, Sweden, 901 85
        • Recruiting
        • Norrlands Universitetssjukhus
        • Contact:
        • Principal Investigator:
          • Mattias Mattsson
      • Uppsala, Sweden, 751 85
        • Recruiting
        • Akademiska Sjukhuset
        • Contact:
        • Principal Investigator:
          • Anders Öberg, MD
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611-2605
        • Terminated
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Terminated
        • Dana-Farber Cancer Institute and Boston Children's Hospital
    • Michigan
      • Grand Rapids, Michigan, United States, 48503
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Medical Group SFC-HEM/ONC
        • Contact:
        • Principal Investigator:
          • Virginia Harrod, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 19 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy
Time Frame: 8 years
Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival rate
Time Frame: 8 years
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
8 years
Progression free survival rate
Time Frame: 8 years
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.
8 years
Toxicity
Time Frame: 8 years
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.
8 years
Feasibility
Time Frame: 6 years
To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
6 years
Quality of life
Time Frame: 8 years
Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
8 years
Prognostic factors
Time Frame: 8 years
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.
8 years
Angiogenic factors
Time Frame: 8 years
To evaluate serum markers for in-vitro correlative studies of tumor response.
8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Andreas Peyrl, MD, Medical University of Vienna
  • Study Chair: Monika Chocholous, MD, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2014

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

May 17, 2011

First Submitted That Met QC Criteria

May 18, 2011

First Posted (Estimated)

May 19, 2011

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 27, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MUV-MEMMAT-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Medulloblastoma Recurrent

Clinical Trials on Bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Denmark

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe