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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Andreas Peyrl, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01356290
First received: May 17, 2011
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
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 liposomal 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 Intervention Phase
Medulloblastoma
Drug: Bevacizumab
Drug: Thalidomide
Drug: Celecoxib
Drug: Fenofibric acid
Drug: Etoposide
Drug: Cyclophosphamide
Drug: Etoposide phosphate
Drug: Liposomal cytarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.

  • Quality of life [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).

  • Prognostic factors [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.


Estimated Enrollment: 40
Study Start Date: April 2014
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
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: Liposomal cytarabine
    25-35mg, intrathecal, every four weeks, alternating with intrathecal etoposide phosphate, 1 year
  Eligibility

Ages Eligible for Study:   up to 19 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01356290

Contacts
Contact: Andreas Peyrl, MD +43 1 40400 ext 32320 andreas.peyrl@meduniwien.ac.at
Contact: Irene Slavc, MD +43 1 40400 ext 32320 irene.slavc@meduniwien.ac.at

Locations
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    Joanne_Kennedy1@dfci.harvard.edu   
Principal Investigator: Mark Kieran, MD, PhD         
Austria
Medical University of Graz Recruiting
Graz, Austria, 8036
Contact: Elisabeth Hulla-Gumbsch    +43 316 385 ext 82686    elisabeth.hulla-gumbsch@klinikum-graz.at   
Principal Investigator: Christian Urban, MD         
Medical University of Innsbruck Recruiting
Innsbruck, Austria, 6020
Contact: Yvonne Ennemoser, MSc    +43 512 504 ext 23605    yvonne.ennemoser@tirol-kliniken.at   
Principal Investigator: Bernhard Meister, MD         
Kepler Universitätsklinikum Med Campus IV Recruiting
Linz, Austria, 4020
Contact: Martina Winkler    +43 5 7680 84 ext 24302    martina.winkler@gespag.at   
Principal Investigator: Georg Ebetsberger, MD         
Salzburger Universitätsklinikum Recruiting
Salzburg, Austria, 5020
Contact: Agnes Gamper, MD    +43 662 448257 ext 759    a.gamper@salk.at   
Principal Investigator: Agnes Gamper, MD         
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Andreas Peyrl, MD    +43 1 40400 ext 32320    andreas.peyrl@meduniwien.ac.at   
Contact: Irene Slavc, MD    +43 1 40400 ext 32320    irene.slavc@meduniwien.ac.at   
Principal Investigator: Andreas Peyrl, MD         
Sub-Investigator: Irene Slavc, MD         
Czech Republic
University Hospital Brno Recruiting
Brno, Czech Republic, 61300
Contact: Alexandra Martincekova, MD    +420532234755    Martincekova.Alexandra@fnbrno.cz   
Principal Investigator: Jaroslav Sterba, MD         
Motol University Hospital Prague Recruiting
Prague, Czech Republic, 15006
Contact: Klara Hruba    +42 0224436401    klara.hruba@fnmotol.cz   
Principal Investigator: David Sumerauer, MD         
Denmark
University hospital Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Karsten Nysom, MD    +45 3545 0809    karsten.nysom@regionh.dk   
Principal Investigator: Karsten Nysom, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Andreas Peyrl, MD Medical University of Vienna
Study Chair: Monika Chocholous, MD Medical University of Vienna
  More Information

Responsible Party: Andreas Peyrl, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01356290     History of Changes
Other Study ID Numbers: MUV-MEMMAT-01 
Study First Received: May 17, 2011
Last Updated: July 28, 2016
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Medulloblastoma
Relapse
Children
antiangiogenic
metronomic
intrathecal

Additional relevant MeSH terms:
Medulloblastoma
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
Bevacizumab
Thalidomide
Etoposide phosphate
Cyclophosphamide
Etoposide
Cytarabine
Celecoxib
Fenofibric acid
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016