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
- subfertility (FSH > 15 IU/L)
- endocrine deficits (hormone supplementation necessary)
- 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
- presence, duration, and therapy of hydrocephalus symptoms (pre- and post-operatively)
- presence of posterior fossa syndrome (cerebellar mutism survey after surgery, before radiotherapy)
- cerebellar symptoms (brief ataxia rating scales 2 and 5 years after diagnosis and age of 18 years)
- 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:
- HUI3 (health status)
- BRIEF (executive functions)
- SDQ (behavioural outcome)
- PedsQL (quality of life)
- QLQ-C30 (quality of life)
- MEES (neurological function, educational provision)
- 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