Clinical trial NCT01356290: Antiangiogenic Therapy for Children with Recurrent Medulloblastoma, Ependymoma and ATRT
Official title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children with Recurrent/progressive Medulloblastoma, Ependymoma and ATRT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Medulloblastoma Recurrent
Ependymoma Recurrent
ATRT Recurrent
Keywords: Medulloblastoma
Ependymoma
ATRT
Relapse
Children
antiangiogenic
metronomic
intraventricular
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2011-05-19
Enrollment: 100
Sex: ALL
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 3 Strata (medulloblastoma - 40 patients; ependymoma - 30 patients; ATRT - 30 patients)
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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

Primary outcomes:
measure: Efficacy
timeFrame: 8 years
Secondary outcomes:
measure: Overall survival rate
timeFrame: 8 years
measure: Progression free survival rate
timeFrame: 8 years
measure: Toxicity
timeFrame: 8 years
measure: Feasibility
timeFrame: 6 years
measure: Quality of life
timeFrame: 8 years
measure: Prognostic factors
timeFrame: 8 years
measure: Angiogenic factors
timeFrame: 8 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute and Boston Children's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Austin
country: United States
facility: Dell Children's Medical Group SFC-HEM/ONC
state: Texas
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Med Campus IV
city: Salzburg
country: Austria
facility: Salzburger Universitätsklinikum
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brno
country: Czech Republic
facility: University Hospital Brno
city: Prague
country: Czech Republic
facility: Motol University Hospital Prague
city: Copenhagen
country: Denmark
facility: University hospital Rigshospitalet
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Bergen
country: Norway
facility: Onkologisk-hematologisk seksjon Barneklinikken Haukeland universitetssjukehus
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Universitetssjukhuset Linköping
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
Study officials:
affiliation: Medical University of Vienna
name: Andreas Peyrl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Vienna
name: Monika Chocholous, MD
role: STUDY_CHAIR
References:
citation: Slavc I, Mayr L, Stepien N, Gojo J, Aliotti Lippolis M, Azizi AA, Chocholous M, Baumgartner A, Hedrich CS, Holm S, Sehested A, Leblond P, Dieckmann K, Haberler C, Czech T, Kool M, Peyrl A. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach. Cancers (Basel). 2022 Oct 19;14(20):5128. doi: 10.3390/cancers14205128.