Recruiting
Phase 2

Antiangiogenic Therapy

Sponsor:

Medical University of Vienna

Code:

NCT01356290

Conditions

Medulloblastoma Recurrent

Ependymoma Recurrent

ATRT Recurrent

Rare CNS Tumor Recurrent

Eligibility Criteria

Sex: All

Age: 0 - 19

Healthy Volunteers: Not accepted

Interventions

Bevacizumab

Thalidomide

Celecoxib

Fenofibric acid

Etoposide

Study Details

Brief summary:

Patients with with recurrent or progressive medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor (ATRT), and CNS tumors of various histologies have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities.

Antiangiogenesis therapy has emerged as a new treatment option in solid malignancies. The frequent delivery of low doses of chemotherapy, referred to as metronomic or antiangiogenic chemotherapy, targets endothelial cells while reducing the toxicity associated with standard dose chemotherapy.

The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma, ATRT, and CNS tumors of various histologies, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life.

The study will be conducted in independent strata. Stratum I (recurrent medulloblastoma): recently completed (Peyrl, 2023). Stratum II (recurrent ependymoma), III (recurrent ATRT) and V (recurrent CNS tumors of various histologies, patients with exclusion criteria and adult patients): The primary objective is to determine the response rate defined as the percentage of patients with complete response (CR), partial response (PR), stable disease (SD) or lack of recurrence at 6 months after start of antiangiogenic treatment. Stratum IV (recurrent medulloblastoma): To determine whether temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt can increase the response rate after 6 months of treatment, compared with etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt. Additionally, PFS, OS, toxicity, QoL, performance status, predictive and prognostic markers will be examined.

In stratum II and III, the study will follow an open label, single arm phase 2 design, and an open label randomized two-arm phase 2 design in Stratum IV, and the exploratory Stratum V.

Conditions

Medulloblastoma Recurrent

Ependymoma Recurrent

ATRT Recurrent

Rare CNS Tumor Recurrent

Study ID

NCT01356290

Start date

Apr, 2014

Status verified date

Oct, 2026

Completion date

Apr, 2030

Anticipated

Primary completion date

Apr, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 19

Healthy Volunteers: Not accepted

Inclusion criteria for patients

  • Stratum I: Relapsed or progressive medulloblastoma - completed
  • Stratum II: Relapsed or progressive ependymoma (at least one site of untreated recurrent disease)
  • Stratum III: Relapsed or progressive ATRT (at least one site of untreated recurrent disease)
  • Stratum IV: Relapsed or progressive medulloblastoma (at least one site of untreated recurrent disease)
  • Stratum V: Relapsed or progressive CNS tumor of various histologies or patients with exclusion criteria or adult patients (explorative)
  • Histological confirmation at diagnosis or relapse Stratum IV: Confirmation of the medulloblastoma group by methylation; IDAT (Intensity Data; raw data of methylation array)
  • 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 legal guardian

Exclusion criteria for patients

  • VP- or subdural peritoneal shunt dependency (can be included in Stratum V)
  • Prior treatment with temozolomide/irinotecan (can be included in Stratum V)
  • Active infection, pregnancy or breast feeding
  • Treatment for current relapse (surgery may be performed before MEMMAT 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 controlled 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

Enrollment

232 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Standard Arm (Stratum II, III, IV, V)

Etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt

experimental: Experimental arm (Stratum IV)

Temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt

Interventions

Bevacizumab

10mg/kg, intravenous (iv), biweekly, 2 years

Thalidomide

3mg/kg, oral, daily, 2 years

Celecoxib

50-400mg, oral bid, daily, 2 years

Fenofibric acid

90mg/m2, oral, daily, 2 years

Etoposide

35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

Cyclophosphamide

2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

Etoposide

0.5mg, intraventricular, day 1-5, every four weeks, alternating with intraventricular cytarabine, 2 years

Cytarabine

16-30mg, intraventricular twice weekly for two weeks out of every four weeks, alternating with intraventricular etoposide phosphate, 2 years

Temozolomide (TMZ)

Stratum IV; 150mg/m2, day 1-5 every four weeks, 1 year

Irinotecan

Stratum IV; 50mg/m2, day 1-5 every four weeks, 1 year

Primary outcome measure

  • Efficacy [ Time Frame: 8 years ]

Central Contacts and Locations

Central contacts

Andreas Peyrl, MD

+43 1 40400andreas.peyrl@meduniwien.ac.at

Johannes A Gojo, MD, PhD

+43 1 40400johannes.gojo@meduniwien.ac.at

Locations

Helen DeVos Children's Hospital

Recruiting

Grand Rapids, Michigan, United States, 48503

Contacts

Rebecca Loret de Mola

616 267 0334rebecca.loretdemola@helendevoschildrens.org

Principal Investigator:

Rebecca Loret De Mola, MD

Dell Children's Medical Group SFC-HEM/ONC

Recruiting

Austin, Texas, United States, 78723

Contacts

Ashley Ratcliffe

512 628 1900aeRatcliff@ascension.org

Principal Investigator:

Virginia Harrod, MD

More Information

Sponsor

Medical University of Vienna

Last update posted

Oct 13, 2026

Last verified

Oct, 2026

Keywords

  • Medulloblastoma
  • Ependymoma
  • ATRT
  • Relapse
  • Children
  • antiangiogenic
  • metronomic
  • intraventricular
  • Rare CNS tumor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Medical University of Vienna on 2026-10-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.