Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma

Summary

Medulloblastoma is a rare brain malignancy, mainly affecting children. Treatment of this rapidly growing tumor begins with maximal surgical removal plus radiation and chemotherapy. Treatment toxicity is high. Post-pubertal and pediatric medulloblastomas are biologically and prognostically different, which mandates age-adapted treatment strategies. Patients after puberty bear an intermediate to high prognostic risk. This means that a large number of these patients, are faced with death and/or disability (mainly neurocognitive). Therefore, the scientific and medical need is high. One of the genetic subgroups of medulloblastoma, the SHH-subgroup (Sonic HedgeHog- subgroup), is highly overrepresented in medulloblastoma patients after puberty. This subgroup can be treated with a targeted therapy. The investigators will therefore randomize patients and treat SHH-subgroup patients with sonidegib and a reduction of radiotherapy dose in the experimental arm of the trial. The hypothesis that this personalized risk-adapted therapy will improve outcomes in view of increased efficacy and decreased toxicity.

Conditions

• Medulloblastoma

Interventions

DRUG

Sonidegib

Sonidegib is a selective smoothened inhibitor that inhibits the sonic hedgehog-signaling pathway. It is used in patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

DRUG

Cisplatin

Cisplatin (CIS) is a platinum derivate used in the treatment in several epithelial tumours. The application route is through the veins.

DRUG

Lomustine

Lomustine is a nitrosourea used in the treatment of brain tumours and Hodgkin's disease. The application route is oral.

DRUG

Vincristine

Vincristine sulfate (VCR) is an inhibitor of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Vincristine sulfate is indicated in acute leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor. The application route is through the vein.

RADIATION

radiotherapy

Radiotherapy to the cranio-spinal axis of 35.2 Gy in 22 daily fractions of 1.6 Gy, followed by an additional boost to the tumour site of 19.8 Gy in 11 daily fractions of 1.8 Gy, summing up to a total dose of 55.0 Gy in 33 daily fractions of 1.6/1.8 Gy.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC

  lead NETWORK

Principal Investigators

• Peter Hau · EORTC study coordinator

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-11

Primary Completion

2025-06-16

Completion

2025-09-10

FDA Drug

Yes

Countries

• Australia
• Austria
• France
• Germany
• Italy
• Netherlands
• Spain
• Switzerland

Study Locations