Clinical Trial: Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma

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 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.

Detailed Summary:
Sponsor: Medical University of Vienna

Current Primary Outcome: Efficacy [ Time Frame: 8 years ]

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


Original Primary Outcome: Efficacy [ Time Frame: 7 years ]

Response rate (=[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment


Current Secondary Outcome:

  • 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
  • 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.
  • 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.
  • Feasibility [ Time Frame: 6 years ]
    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 ]
    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 ]
    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 ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.


Original Secondary Outcome:

  • Overall survival rate [ Time Frame: 7 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
  • Progression free survival rate [ Time Frame: 7 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.
  • Toxicity [ Time Frame: 7 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.
  • Feasibility [ Time Frame: 5 years ]
    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 ]
    QoL will be evaluated by the KINDL®- questionnaire.
  • Prognostic factors [ Time Frame: 7 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.
  • Angiogenic factors [ Time Frame: 7 years ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.


Information By: Medical University of Vienna

Dates:
Date Received: May 17, 2011
Date Started: April 2014
Date Completion: April 2022
Last Updated: May 15, 2017
Last Verified: May 2017