Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (PNET4)

NCT01351870 | Completed Phase 3 DMC

• 1 other identifier: IC2003-06
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is an international prospective randomised trial, which will compare two radiotherapy regimens in children and adolescents (aged 4 or 5 years to 21 years inclusive) with carefully staged 'standard risk' medulloblastoma.

Conditions

Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• Free survival rate

  To compare in a randomised trial the event free survival rate for children and adolescents with standard risk medulloblastoma treated with either hyperfractionated radiotherapy or reduced dose radiotherapy with conventional fractionation.

  2 years after the start of the study

Secondary Outcomes (3)

• To compare overall survival between the two treatment arms.

  Follow-up of the last patient included up to the age of 20 years

• To compare the pattern of relapse between the two treatment arms

  Follow-up of the last patient included up to the age of 20 years

• To explore the benefit and the risks of neurosurgery

  Follow-up of the last patient included up to the age of 20 years

Study Arms (2)

Standard Fractionation Regimen

ACTIVE COMPARATOR

1.8 Gy daily, 5 fractions per week Cranio-spinal axis: 23.4 Gy in 13 fractions of 1.8 Gy Posterior fossa: 30.6 Gy in 17 fractions of 1.8 Gy

Radiation: Standard Fractionation Regimen

Hyperfractionated radiotherapy

EXPERIMENTAL

1 Gy b.d. (minimum interval between fractions 8 hours). 10 fractions per week Craniospinal axis: 36 Gy in 36 fractions of 1 Gy Posterior fossa: 24 Gy in 24 fractions of 1 Gy Tumour Bed: 8 Gy in 8 fractions of 1 Gy

Radiation: Hyperfractionated Radiotherapy

Interventions

Standard Fractionation Regimen RADIATION

1.8 Gy daily, 5 fractions per week Cranio-spinal axis: 23.4 Gy in 13 fractions of 1.8 Gy Posterior fossa: 30.6 Gy in 17 fractions of 1.8 Gy

Standard Fractionation Regimen

Hyperfractionated Radiotherapy RADIATION

1 Gy b.d. (minimum interval between fractions 8 hours). 10 fractions per week Craniospinal axis: 36 Gy in 36 fractions of 1 Gy Posterior fossa: 24 Gy in 24 fractions of 1 Gy Tumour Bed: 8 Gy in 8 fractions of 1 Gy

Hyperfractionated radiotherapy

Eligibility Criteria

• Age: 4 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age at diagnosis at least 4 years or 5 years (according to the policy of the National Brain Tumour Group) and less than 22 years.
• Histologically proven medulloblastoma, including the following variants(WHO classification - 2000): classic medulloblastoma, nodular / desmoplastic medulloblastoma, melanotic medulloblastoma, medullomyoblastoma No CNS metastasis on MRI - supratentorial, arachnoid of the posterior fossa or spine.
• No clinical evidence of extra-CNS metastasis
• No tumour cells on the cytospin of lumbar CSF. Central Review of CSF cytology is recommended but not mandatory. It will be left to national policy.
• Radiotherapy to start no more than 40 days after surgery.
• Ability to receive twice daily radiotherapy.
• Vital functions within normal range for their age group.
• CTC grades \< 2 for liver, renal, haematological and audiological function.
• No medical contraindication to radiotherapy or chemotherapy.
• Written informed consent (and patient assent where appropriate) according to the laws of each participating country. Written informed consent should also be sought for biological studies.
• National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).

You may not qualify if:

• Brainstem or supratentorial primitive neuroectodermal tumour.
• Atypical teratoid rhabdoid tumour.
• Medulloepithelioma.
• Ependymoblastoma.
• Large cell médulloblastoma.
• Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF).
• Patient previously treated for a brain tumour or any type of malignant disease.
• Patients who are pregnant.
• Females who are sexually active and not taking reliable contraception.
• Known predisposition to medulloblastoma e.g. Gorlin's syndrome.

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

Related Publications (1)

• Goschzik T, Schwalbe EC, Hicks D, Smith A, Zur Muehlen A, Figarella-Branger D, Doz F, Rutkowski S, Lannering B, Pietsch T, Clifford SC. Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT/non-SHH medulloblastoma: a retrospective, molecular analysis of the HIT-SIOP PNET 4 trial. Lancet Oncol. 2018 Dec;19(12):1602-1616. doi: 10.1016/S1470-2045(18)30532-1. Epub 2018 Nov 1.

  PMID: 30392813 DERIVED

MeSH Terms

Conditions

Medulloblastoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• DOZ François, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2011
• First Posted: May 11, 2011
• Study Start: April 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: March 1, 2020
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (1)