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NCT Number: NCT01356290

Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors

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.

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Key information

Conditions

Medulloblastoma Recurrent ATRT Recurrent Disease Attributes Ependymoma Ependymoma Recurrent Glioma Medulloblastoma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Pathologic Processes Pathological Conditions, Signs and Symptoms Rare CNS Tumor Recurrent Recurrence

Age range

Up to 19 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medical University of Graz, Graz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Bevacizumab

Drug

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

thalidomide

Drug

3mg/kg, oral, daily, 2 years

Celecoxib

Drug

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

Fenofibric acid

Drug

90mg/m2, oral, daily, 2 years

etoposide

Drug

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

Cyclophosphamide

Drug

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

Cytarabine

Drug

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

Temozolomide (TMZ)

Drug

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

Irinotecan

Drug

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

Primary outcomes

  1. Efficacy

    Time frame: 8 years

    Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment

Secondary outcomes

  1. Overall survival rate

    Time frame: 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

  2. Progression free survival rate

    Time frame: 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.

  3. Toxicity

    Time frame: 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.

  4. Feasibility

    Time frame: 6 years

    To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.

  5. Quality of life

    Time frame: 8 years

    Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).

  6. Prognostic factors

    Time frame: 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.

  7. Angiogenic factors

    Time frame: 8 years

    To evaluate serum markers for in-vitro correlative studies of tumor response.

Interested in participating?

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Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Registry information

Official study title

A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors

Acronym: MEMMAT

Important dates

Study start
2014
Primary completion
2030
Study completion
2030
First posted
May 19, 2011
Registry last updated
Sep 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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