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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Medical University of Vienna
Sponsor:
Collaborators:
Medical University of Graz
Medical University Innsbruck
General Hospital Linz
Salzburger Landeskliniken
Information provided by (Responsible Party):
Andreas Peyrl, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01356290
First received: May 17, 2011
Last updated: April 14, 2014
Last verified: April 2014

May 17, 2011
April 14, 2014
April 2014
April 2019   (final data collection date for primary outcome measure)
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
Efficacy [ Time Frame: 7 years ] [ Designated as safety issue: No ]
Response rate (=[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
Complete list of historical versions of study NCT01356290 on ClinicalTrials.gov Archive Site
  • 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.
  • Overall survival rate [ Time Frame: 7 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: 7 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: 7 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: 5 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: 7 years ] [ Designated as safety issue: No ]
    QoL will be evaluated by the KINDL®- questionnaire.
  • Prognostic factors [ Time Frame: 7 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: 7 years ] [ Designated as safety issue: No ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.
Not Provided
Not Provided
 
Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma
A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Medulloblastoma
  • 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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
April 2022
April 2019   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Relapsed or progressive medulloblastoma
  • Histological confirmation of medulloblastoma at diagnosis or relapse
  • Female or male, aged from 0 to <20 years (at time of initial diagnosis)
  • Adequate renal, hepatic, cardiac, pulmonary and bone marrow function
  • 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
  • Irradiation or conventional chemotherapy for current relapse (surgery may be performed before antiangiogenic treatment)
  • Known hypersensitivity to any of the drugs in the protocol
  • Active peptic ulcer
  • Any significant cardiovascular disease 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
Both
up to 19 Years
No
Contact: Andreas Peyrl, MD +43 1 40400 ext 3232 andreas.peyrl@meduniwien.ac.at
Contact: Irene Slavc, MD +43 1 40400 ext 3232 irene.slavc@meduniwien.ac.at
Austria
 
NCT01356290
MUV-MEMMAT-01
Yes
Andreas Peyrl, Medical University of Vienna
Medical University of Vienna
  • Medical University of Graz
  • Medical University Innsbruck
  • General Hospital Linz
  • Salzburger Landeskliniken
Principal Investigator: Andreas Peyrl, MD Medical University of Vienna
Study Chair: Monika Chocholous, MD Medical University of Vienna
Medical University of Vienna
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP