In this study, we investigate whether personalized, risk-adjusted therapy improves therapy outcomes and reduces toxicity in post-pubertal patients with medulloblastoma.

We further hypothesize that clinical, magnetic resonance imaging (MRI) and voxel-based radiotherapy planning data as well as biomarkers extracted from liquid biopsies and tumour tissue samples can be processed in a way that allows to improve diagnosis and treatment and to reduce toxicity. 

Primary objective: 

• To compare progression-free survival (PFS) by central review of a personalized intensity-modulated therapy (experimental arm; sonidegib) vs. standard therapy (modified NOA-07) in the SHH-activated subgroup in post-pubertal patients with newly diagnosed standard risk medulloblastoma 

Secondary objectives: 

In experimental versus standard arm and in 3 molecular subgroups separately (except otherwise stated):

• Comparison of PFS in WNT and Group 4 subgroups
• Comparison of the PFS in the molecular subgroups
• Comparison of overall survival (OS) in the molecular subgroups
• Evaluation of the safety and tolerability profile
• Assessment of short- and long-term health-related quality of life (HRQoL)
• Assessing issues related to survival
• Assessment of short- and long-term neurocognitive function (NCF)
• Assessment of short- and long-term endocrine function
• Evaluation of the incidence of secondary malignancies

Descriptive objectives:

Response, PFS, OS, safety and tolerability, NCF and HRQoL in the standard arm of the pooled subgroups

Exploratory objectives:

• To report response, PFS, OS, safety and tolerability, NCF and HRQoL in the standard arm of pooled subgroups
• To compare response, PFS, Event Free Survival (EFS), OS and toxicity data of post-pubertal and adult patients with medulloblastoma treated in this study vs. patients treated in the PNET5 study
• To evaluate the association between NCF and HRQoL over time
• To describe the difference in safety and tolerability, maintenance chemotherapy delivery, HRQoL, neurocognitive function, survivorship, and endocrine /fertility function between proton- and photon-based cranio-spinal radiotherapy

To describe the difference in safety and tolerability, maintenance chemotherapy delivery, HRQoL, neurocognitive function, survivorship, and endocrine /fertility function between 35.2 Gy and 23.4 Gy as part of the cranio-spinal radiotherapy 

Further information and the study centers for the EORTC 1634 can be found in the attached documents.