MEMMAT: Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT
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. This study will evaluate the use of biweekly IV administration of bevacizumab in combination with five drugs taken orally (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. The goal of this study is to provide additional 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 previously treated children and young adults. Progression-free survival (PFS), overall survival (OS), as well as feasibility and toxicity will be examined.
Trial Information
Screening–Doctors will review the patient’s medical history to make sure that this study treatment is appropriate
Treatment – Treatment can take up to 12 months if the cancer does not continue to grow, and there are no unacceptable side effects.
Approach
Treatment:
a. Intravenous (IV medications)
Bevacizumab (Avastin) – given biweekly
b. Oral
Thalidomide – given daily
Celecoxib – given daily
Fenofibric acid – given daily
Etoposide
Cylclophosphamide
c. Intrathecal
Etoposide phosphate - given twice weekly, 2 out of every 4 weeks alternating with cytarabine
Cytarabine – given twice weekly, 2 out of every 4 weeks alternating with etoposide phosphate
Additional Information
NCT01356290
View on ClinicalTrials.gov
Eligibility
Inclusion Criteria
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 the time of original diagnosis)
Labs confirming adequate organ and bone marrow function
Karnofsky performance status ≥50. For infants and children 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).
Patients that have received a allogeneic hematopoietic stem cell transplant are not eligible
Known hypersensitivity to any of the drugs in the protocol
Active peptic ulcer
Any significant cardiovascular disease not controlled by standard therapy (e.g. systemic hypertension)
Anticipated need for major elective surgery during the course of study treatment
Any disease/condition that contraindicates the use of 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
Contact Information
Study Contact: Andreas Peryl, MD
University of Vienna
Email: andreas.peyrl@meduniwien.ac.at
Phone: +43 1 40400 ext 32320
Study Contact: Irene Slavc, MD
Email: irene.slavc@meduniwien.ac.at
Phone: +43 1 40400 ext 32320