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

Status:	Recruiting
Conditions:	Brain Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	Any - 19
Updated:	9/2/2018
Start Date:	April 2014
End Date:	April 2023
Contact:	Andreas Peyrl, MD
Email:	andreas.peyrl@meduniwien.ac.at
Phone:	+43 1 40400

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
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.

Inclusion Criteria:

- Relapsed or progressive medulloblastoma (at least one site of untreated recurrent
disease)

- Histological confirmation of medulloblastoma 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

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)

- 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

We found this trial at

sites

Ann & Robert H. Lurie Children's Hospital of Chicago

225 E Chicago Ave
Chicago, Illinois 60611

(312) 227-4000