Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma (MEMMAT)
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.
Drug: Fenofibric acid
Drug: Etoposide phosphate
Drug: Liposomal cytarabine
|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|
- 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
- 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.
|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)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01356290
|Contact: Andreas Peyrl, MD||+43 1 40400 ext email@example.com|
|Contact: Irene Slavc, MD||+43 1 40400 ext firstname.lastname@example.org|
|Department of Pediatrics, Medical University of Vienna||Recruiting|
|Vienna, Austria, 1090|
|Contact: Andreas Peyrl, MD +43 1 40400 ext 3232 email@example.com|
|Contact: Irene Slavc, MD +43 1 40400 ext 3232 firstname.lastname@example.org|
|Principal Investigator: Andreas Peyrl, MD|
|Principal Investigator:||Andreas Peyrl, MD||Medical University of Vienna|
|Study Chair:||Monika Chocholous, MD||Medical University of Vienna|