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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01356290
Recruitment Status : Recruiting
First Posted : May 19, 2011
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Andreas Peyrl, Medical University of Vienna

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Medulloblastoma Drug: Bevacizumab Drug: Thalidomide Drug: Celecoxib Drug: Fenofibric acid Drug: Etoposide Drug: Cyclophosphamide Drug: Etoposide phosphate Drug: Cytarabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma
Study Start Date : April 2014
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine



Intervention Details:
  • 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


Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01356290


Contacts
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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

Locations
Show Show 21 study locations
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Andreas Peyrl, MD Medical University of Vienna
Study Chair: Monika Chocholous, MD Medical University of Vienna
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Responsible Party: Andreas Peyrl, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01356290    
Other Study ID Numbers: MUV-MEMMAT-01
First Posted: May 19, 2011    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Keywords provided by Andreas Peyrl, Medical University of Vienna:
Medulloblastoma
Relapse
Children
antiangiogenic
metronomic
intrathecal
Additional relevant MeSH terms:
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Medulloblastoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cytarabine
Thalidomide
Celecoxib
Cyclophosphamide
Bevacizumab
Etoposide
Etoposide phosphate
Fenofibric acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents