Clinical Trial: International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An International Prospective Study on Clinically Standard-risk Medulloblastoma in Children Older Than 3 to 5 Years With Low-risk Biological Profile (PNET 5 MB-LR) or Avera

Brief Summary: The study PNET 5 MB has been designed for children with medulloblastoma of standard risk (according to the risk-group definitions which have been used so far; e.g. in PNET 4). With the advent of biological parameters for stratification into clinical medulloblastoma trials, the ß-catenin status will be the only criterion according to which study patients will be assigned to either treatment arm PNET 5 MB - LR or to PNET 5 MB - SR, respectively. The initial diagnostic assessments (imaging, staging, histology, and tumor biology) required for study entry are the same for both treatment arms.

Detailed Summary:

The aim of the LR-treatment arm is to confirm the high rate of event-free survival in patients between the ages of 3 to 5 years and less than 22, with 'standard risk' medulloblastoma with a low-risk biological profile. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by immuno-histochemistry (IHC). Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 18.0 Gy to the craniospinal axis. Following radiotherapy, patients will receive a reduced-intensity chemotherapy with a total of 6 cycles of chemotherapy consisting of 3 courses of cisplatin, CCNU and vincristine alternating with 3 courses of cyclophosphamide and vincristine.

The aim of the SR-arm is to test whether concurrent carboplatin during radiotherapy followed by 8 cycles of maintenance chemotherapy in patients with 'standard risk' medulloblastoma with an average-risk biological profile may improve outcome. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC. Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 23.4 Gy to the craniospinal axis. Following radiotherapy, patients will receive a modified-intensity chemotherapy with a total of 8 cycles of chemotherapy consisting of 4 courses of cisplatin, CCNU and vincristine alternating with 4 courses of cyclophosphamide and vincristine.


Sponsor: Universitätsklinikum Hamburg-Eppendorf

Current Primary Outcome: 3-year Event-Free Survival (EFS) [ Time Frame: LR-arm after 9 years, SR-arm after 105 events (approx. 10 years) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Overall survival [ Time Frame: 10 years ]
  • Pattern of relapse [ Time Frame: 10 years ]

    Defined in 5 categorical variables:

    no relapse, local relapse, distant relapse, local and distant relapse, death

  • Late effects of therapy on endocrine function [ Time Frame: 10 years ]

    measured as

    1. subfertility (FSH > 15 IU/L)
    2. endocrine deficits (hormone supplementation necessary)
    3. growth retardation (calculated as the difference in height standard deviation score from diagnose) 2 and 5 years after diagnosis and age of 18 years
  • Late effects of therapy on audiology [ Time Frame: 8 years ]
    measured on audiogram performed 2 years after diagnosis, grading according to Chang ototoxicity grading (Chang and Chinosornvatana 2010)
  • Late effects of therapy on neurology [ Time Frame: 10 years ]

    Measured as

    1. presence, duration, and therapy of hydrocephalus symptoms (pre- and post-operatively)
    2. presence of posterior fossa syndrome (cerebellar mutism survey after surgery, before radiotherapy)
    3. cerebellar symptoms (brief ataxia rating scales 2 and 5 years after diagnosis and age of 18 years)
    4. presence of symptoms for brain nerve dysfunction (2 and 5 years after diagnosis and age of 18 years)
  • Late effects of therapy on quality of survival [ Time Frame: 10 years ]

    measured with standardized questionnaires/ scores:

    1. HUI3 (health status)
    2. BRIEF (executive functions)
    3. SDQ (behavioural outcome)
    4. PedsQL (quality of life)
    5. QLQ-C30 (quality of life)
    6. MEES (neurological function, educational provision)
    7. MFI (fatigue) 2 and 5 years after diagnosis and age of 18 years
  • Progression-free survival [ Time Frame: 10 years ]
  • Feasibility of carboplatin treatment [ Time Frame: approx. 7 years ]
    measured as timely delivery of chemotherapy number of interruptions days during radiotherapy toxicities within 8 weeks after end of radiotherapy
  • Residual tumor [ Time Frame: 6 years ]
    measured by central MRI review postoperatively
  • Leukoencephalopathy grading [ Time Frame: 8 years ]
    measured 2 years after diagnosis grades 0, 1, 2, 3, 4


Original Secondary Outcome: Same as current

Information By: Universitätsklinikum Hamburg-Eppendorf

Dates:
Date Received: February 7, 2014
Date Started: June 2014
Date Completion: April 2024
Last Updated: May 5, 2017
Last Verified: May 2017