Clinical Trials /

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

NCT01356290

Description:

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.

Related Conditions:
  • Medulloblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma
  • Official Title: A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma

Clinical Trial IDs

  • ORG STUDY ID: MUV-MEMMAT-01
  • NCT ID: NCT01356290

Conditions

  • Medulloblastoma

Interventions

DrugSynonymsArms
BevacizumabAvastin
Thalidomide
Celecoxib
Fenofibric acid
Etoposide
Cyclophosphamide
Etoposide phosphate
Liposomal cytarabine

Purpose

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 liposomal 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.

Trial Arms

NameTypeDescriptionInterventions

Eligibility 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
      
Maximum Eligible Age:19 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy
Time Frame:8 years
Safety Issue:
Description:Response rate (Complete remission, partial response, stable disease =[CR+PR+SD]/n) 6 months after start of antiangiogenic treatment

Secondary Outcome Measures

Measure:Overall survival rate
Time Frame:8 years
Safety Issue:
Description: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
Measure:Progression free survival rate
Time Frame:8 years
Safety Issue:
Description: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.
Measure:Toxicity
Time Frame:8 years
Safety Issue:
Description: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.
Measure:Feasibility
Time Frame:6 years
Safety Issue:
Description:To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.
Measure:Quality of life
Time Frame:8 years
Safety Issue:
Description:Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).
Measure:Prognostic factors
Time Frame:8 years
Safety Issue:
Description: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.
Measure:Angiogenic factors
Time Frame:8 years
Safety Issue:
Description:To evaluate serum markers for in-vitro correlative studies of tumor response.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Medical University of Vienna

Trial Keywords

  • Medulloblastoma
  • Relapse
  • Children
  • antiangiogenic
  • metronomic
  • intrathecal

Last Updated

April 5, 2017