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Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT (MEMMAT)

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ClinicalTrials.gov Identifier: NCT01356290
Recruitment Status : Recruiting
First Posted : May 19, 2011
Last Update Posted : August 20, 2020
Sponsor:
Information provided by (Responsible Party):
Andreas Peyrl, Medical University of Vienna

Tracking Information
First Submitted Date  ICMJE May 17, 2011
First Posted Date  ICMJE May 19, 2011
Last Update Posted Date August 20, 2020
Study Start Date  ICMJE April 2014
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
Efficacy [ Time Frame: 8 years ]
Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2011)
Efficacy [ Time Frame: 7 years ]
Response rate (=[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
  • 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
  • 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.
  • 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.
  • Feasibility [ Time Frame: 6 years ]
    To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
  • 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).
  • 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.
  • Angiogenic factors [ Time Frame: 8 years ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2011)
  • Overall survival rate [ Time Frame: 7 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
  • Progression free survival rate [ Time Frame: 7 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.
  • Toxicity [ Time Frame: 7 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.
  • Feasibility [ Time Frame: 5 years ]
    To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
  • Quality of life [ Time Frame: 7 years ]
    QoL will be evaluated by the KINDL®- questionnaire.
  • Prognostic factors [ Time Frame: 7 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.
  • Angiogenic factors [ Time Frame: 7 years ]
    To evaluate serum markers for in-vitro correlative studies of tumor response.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT
Official Title  ICMJE A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma and ATRT
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
3 Strata (medulloblastoma, ependymoma, ATRT)
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Medulloblastoma Recurrent
  • Ependymoma Recurrent
  • ATRT Recurrent
Intervention  ICMJE
  • Drug: Bevacizumab
    10mg/kg, intravenous (iv), biweekly, 1 year
    Other Name: Avastin
  • Drug: Thalidomide
    3mg/kg, oral, daily, 1 year
  • Drug: Celecoxib
    50-400mg, oral bid, daily, 1 year
  • Drug: Fenofibric acid
    90mg/m2, oral, daily, 1 year
  • Drug: Etoposide
    35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
  • Drug: Cyclophosphamide
    2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
  • Drug: Etoposide phosphate
    0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year
  • Drug: Cytarabine
    16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2020)
100
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2011)
40
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andreas Peyrl, MD +43 1 40400 ext 32320 andreas.peyrl@meduniwien.ac.at
Contact: Irene Slavc, MD +43 1 40400 ext 32320 irene.slavc@meduniwien.ac.at
Listed Location Countries  ICMJE Austria,   Czechia,   Denmark,   France,   Norway,   Spain,   Sweden,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01356290
Other Study ID Numbers  ICMJE MUV-MEMMAT-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andreas Peyrl, Medical University of Vienna
Study Sponsor  ICMJE Medical University of Vienna
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreas Peyrl, MD Medical University of Vienna
Study Chair: Monika Chocholous, MD Medical University of Vienna
PRS Account Medical University of Vienna
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP