Antiangiogenic Therapy for Children with Recurrent Medulloblastoma, Ependymoma and ATRT
- Conditions
- Medulloblastoma RecurrentATRT RecurrentEpendymoma Recurrent
- Registration Number
- NCT01356290
- Lead Sponsor
- Medical University of Vienna
- Brief Summary
Patients with relapsed medulloblastoma, ependymoma and ATRT 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, ependymoma and ATRT, 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 Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Relapsed or progressive medulloblastoma, ependymoma or ATRT (at least one site of untreated recurrent disease)
- Histological confirmation of medulloblastoma, ependymoma or ATRT 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Efficacy 8 years Response rate (Complete remission, partial response, stable disease =\[CR+PR+SD\]/n) 6 months after start of antiangiogenic treatment
- Secondary Outcome Measures
Name Time Method Overall survival rate 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 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 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.
Quality of life 8 years Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
Feasibility 6 years To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
Prognostic factors 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 8 years To evaluate serum markers for in-vitro correlative studies of tumor response.
Trial Locations
- Locations (22)
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute and Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Dell Children's Medical Group SFC-HEM/ONC
🇺🇸Austin, Texas, United States
Medical University of Graz
🇦🇹Graz, Austria
Salzburger Universitätsklinikum
🇦🇹Salzburg, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
University Hospital Brno
🇨🇿Brno, Czech Republic
Motol University Hospital Prague
🇨🇿Prague, Czech Republic
University hospital Rigshospitalet
🇩🇰Copenhagen, Denmark
Centre Oscar Lambret
🇫🇷Lille, France
Centre Léon Bérard
🇫🇷Lyon, France
Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
🇳🇴Bergen, Norway
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Universitetssjukhuset Linköping
🇸🇪Linköping, Sweden
Skånes universitetssjukhus
🇸🇪Lund, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Medical University of Innsbruck
🇦🇹Innsbruck, Austria
Kepler Universitätsklinikum Med Campus IV
🇦🇹Linz, Austria
Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Akademiska sjukhuset
🇸🇪Uppsala, Sweden