medulloblastoma
Conditions
Interventions
1. patients with SHH-activated medulloblastoma without metastases (M0) or with
only microscopic metastases in the CSF (M1) will be randomised between standard
chemotherapy (modified NOA-7) combined
Sponsors
European Organisation for Research in Treatment of Cancer (EORTC)
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: •Newly diagnosed, histologically proven, genetically classified, centrally confirmed medulloblastoma (WNT M0-1, SHH (p53wt) M0-1, Group 4 M0-1) • Molecular subtype: medulloblastoma, SHH-activated and TP53-wildtype, M0-1; medulloblastoma, WNT-activated, M0-1; medulloblastoma, Group 4, M0-1 • Histologic subtype: medulloblastoma, classic (CMB); medulloblastoma, desmoplastic/nodular (DNMB); medulloblastoma, with extensive nodularity (MBEN); medulloblastoma, large cell/anaplastic (LCA) • Adults (>=18 years) in WNT-activated and Group 4 medulloblastoma • Post-pubertal patients (
Exclusion criteria
Exclusion criteria: • Prior treatment for medulloblastoma • Unavailability of central review pathology results • Known prognostic markers (MYC/MYCN amplification, MYC/MYCN mutation) • Patients with germline alterations that are prognostically linked to medulloblastoma (e.g., TP53, PTCH, SUFU, BRCA2, PALB2) and that are already known before randomization will not be eligible. • Inability to start radiotherapy within 43 days after surgery • Significant sensorineural hearing deficit as defined by pure tone audiometry with bone conduction or air conduction and normal tympanogram showing impairment >= 20 dB at 1-3 kHz • Any medical contraindication to radiotherapy or chemotherapy • Hypersensitivity to contrast medium for MRI • Hypersensitivity towards the active substance of any of study drugs or their excipients • Concurrent severe or uncontrolled medical disease (e.g., active systemic infection, diabetes, psychiatric disorder) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study • Prior or second invasive malignancy, except non-melanoma skin cancer, completely resected cervical carcinoma in situ, low risk prostate cancer (cT1-2a N0 and Gleason score
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare progression-free survival (PFS) by central review of a personalized intensity-modulated therapy (experimental arm; sonidegib) vs. standard therapy in the SHH-activated subgroup in post-pubertal patients with newly diagnosed standard risk medulloblastoma. | — |
Secondary
| Measure | Time frame |
|---|---|
| In experimental versus standard arm and in the 3 molecular subgroups separately (except otherwise stated): • To compare PFS by central reviewer in WNT & Group 4 subgroups • To compare PFS by local investigator in 3 molecular subgroups • To compare overall survival (OS) in 3 molecular subgroups • To evaluate safety and tolerability profile • To evaluate short- and long-term health-related quality of life (HRQoL) with a particular emphasis on the social functioning scale • To evaluate issues linked to survivorship (fear of recurrence, having problems with insurance/mortgage, work opportunities, life plans/goals and relationships with family or friends) • To evaluate short- and long-term neurocognitive function (NCF) • To evaluate short- and long-term endocrine function • To assess the incidence of second malignancies | — |
Countries
Netherlands
Outcome results
None listed