Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (SIOP-PNET-4)

Institut Curie

Status and phase: Completed; Phase 3

Conditions: Medulloblastoma

Treatments: Radiation: Hyperfractionated Radiotherapy; Radiation: Standard Fractionation Regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT01351870

IC2003-06 PNET4

Details and patient eligibility

About

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.

Full description

Patients eligible for the study will be those with non-metastatic medulloblastoma (by imaging and CSF cytology) at diagnosis. Patients randomised to the standard arm will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the posterior fossa and 23.4 Gy to the craniospinal axis. The experimental arm will be hyperfractionated (twice a day) radiotherapy (1 Gy b.d.) with a dose of 60 Gy to the posterior fossa with an additional 8 Gy to the tumour bed and 36 Gy to the craniospinal axis. Both groups will receive identical chemotherapy consisting of eight weekly doses of Vincristine given with radiotherapy and 8 courses of CCNU, cisplatin and vincristine following radiotherapy.

Enrollment: 52 patients

Sex: All

Ages: 4 to 22 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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).

Exclusion criteria

• One of the inclusion criteria is lacking.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Standard Fractionation Regimen

Active Comparator group

Description:

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

Treatment:

Radiation: Standard Fractionation Regimen

Hyperfractionated radiotherapy

Experimental group

Description:

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

Treatment:

Radiation: Hyperfractionated Radiotherapy