Working… Menu

Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma (MEMMAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01356290
Recruitment Status : Recruiting
First Posted : May 19, 2011
Last Update Posted : August 27, 2019
Information provided by (Responsible Party):
Andreas Peyrl, Medical University of Vienna

Brief Summary:
Patients with relapsed medulloblastoma 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, 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.

Condition or disease Intervention/treatment Phase
Medulloblastoma Drug: Bevacizumab Drug: Thalidomide Drug: Celecoxib Drug: Fenofibric acid Drug: Etoposide Drug: Cyclophosphamide Drug: Etoposide phosphate Drug: Cytarabine Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma
Study Start Date : April 2014
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Bevacizumab
    10mg/kg, intravenous (iv), biweekly, 1 year
    Other Name: Avastin
  • Drug: Thalidomide
    3mg/kg, oral, daily, 1 year
  • Drug: Celecoxib
    50-400mg, oral bid, daily, 1 year
  • Drug: Fenofibric acid
    90mg/m2, oral, daily, 1 year
  • 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 phosphate
    0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year
  • Drug: Cytarabine
    16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year

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

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. Feasibility [ Time Frame: 6 years ]
    To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.

  5. 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).

  6. 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.

  7. Angiogenic factors [ Time Frame: 8 years ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Relapsed or progressive medulloblastoma (at least one site of untreated recurrent disease)
  • Histological confirmation of medulloblastoma 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01356290

Layout table for location contacts
Contact: Andreas Peyrl, MD +43 1 40400 ext 32320
Contact: Irene Slavc, MD +43 1 40400 ext 32320

Layout table for location information
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611-2605
Contact: Emily Golbeck   
Contact: Kevin Ritt   
Principal Investigator: Stewart Goldman, MD         
Sub-Investigator: Rishi Lulla, MD         
United States, Massachusetts
Dana-Farber Cancer Institute and Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Joanne Kennedy, RN, BA    617-632-5324   
Principal Investigator: Susan Chi, MD         
Medical University of Graz Recruiting
Graz, Austria, 8036
Contact: Elisabeth Hulla-Gumbsch    +43 316 385 ext 82686   
Principal Investigator: Martin Benesch, MD         
Medical University of Innsbruck Recruiting
Innsbruck, Austria, 6020
Contact: Yvonne Ennemoser, MSc    +43 512 504 ext 23605   
Principal Investigator: Roman Crazzolara, MD         
Kepler Universitätsklinikum Med Campus IV Recruiting
Linz, Austria, 4020
Contact: Martina Winkler    +43 5 7680 84 ext 24302   
Principal Investigator: Georg Ebetsberger, MD         
Salzburger Universitätsklinikum Recruiting
Salzburg, Austria, 5020
Contact: Agnes Gamper, MD    +43 662 448257 ext 759   
Principal Investigator: Agnes Gamper, MD         
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Andreas Peyrl, MD    +43 1 40400 ext 32320   
Contact: Irene Slavc, MD    +43 1 40400 ext 32320   
Principal Investigator: Andreas Peyrl, MD         
Sub-Investigator: Irene Slavc, MD         
University Hospital Brno Recruiting
Brno, Czechia, 61300
Contact: Alexandra Martincekova, MD    +420532234755   
Principal Investigator: Jaroslav Sterba, MD         
Sub-Investigator: Zdenek Pavelka, MD         
Motol University Hospital Prague Recruiting
Prague, Czechia, 15006
Contact: Klara Hruba    +42 0224436401   
Principal Investigator: David Sumerauer, MD         
University hospital Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Karsten Nysom, MD    +45 3545 0809   
Principal Investigator: Karsten Nysom, MD         
Centre Oscar Lambret Terminated
Lille, France, 59037
Hospital Infantil Universitario Nino Jesus Recruiting
Madrid, Spain, 28009
Contact: Alvaro Lassaletta, MD, PhD    +34 915 035938 ext 377   
Principal Investigator: Alvaro Lassaletta, MD, PhD         
Sahlgrenska Universitetssjukhuset Recruiting
Göteborg, Sweden, 416 85
Contact: Karin Fritzson    +46 31 343 58 65   
Contact: Anna Schröder- Håkansson    +46 31 343 58 65   
Principal Investigator: Magnus Sabel, MD         
Sub-Investigator: Birgitta Lannering, Prof         
Universitetssjukhuset Linköping Recruiting
Linköping, Sweden, 581 85
Contact: Birgitta Hellström    +46 10 103 13 54   
Contact: Pernilla Augustsson    +46 10-103 13 50   
Principal Investigator: Irene Devenney, MD         
Skånes universitetssjukhus Recruiting
Lund, Sweden, 221 85
Contact: Yvonne Håkansson    +46 46-17 80 64   
Contact: Simon Johansson    +46 46-17 80 64   
Principal Investigator: Helena Mörse, MD         
Karolinska University Hospital Recruiting
Stockholm, Sweden, SE-171 76
Contact: Carina Rinaldo    +46 8 517 701 51   
Contact: Yvonne Copeland    +46 8 517 724 84   
Principal Investigator: Stefan Holm, MD         
Norrlands Universitetssjukhus Recruiting
Umeå, Sweden, 901 85
Contact: Marita Wikström-Larsson    +46 90-785 02 44   
Principal Investigator: Mattias Mattsson         
Akademiska sjukhuset Recruiting
Uppsala, Sweden, 751 85
Contact: Katarina Vallin    +46 18 611 34 94   
Principal Investigator: Anders Öberg, MD         
Sponsors and Collaborators
Medical University of Vienna
Layout table for investigator information
Principal Investigator: Andreas Peyrl, MD Medical University of Vienna
Study Chair: Monika Chocholous, MD Medical University of Vienna

Layout table for additonal information
Responsible Party: Andreas Peyrl, MD, Medical University of Vienna Identifier: NCT01356290     History of Changes
Other Study ID Numbers: MUV-MEMMAT-01
First Posted: May 19, 2011    Key Record Dates
Last Update Posted: August 27, 2019
Last Verified: August 2019
Keywords provided by Andreas Peyrl, Medical University of Vienna:
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide phosphate
Fenofibric acid
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents