Clinical trial NCT01351870: Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
Official title: A Prospective Randomised Controlled Trial of Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Medulloblastoma
Lead sponsor: Institut Curie
Sponsor class: OTHER
First posted: 2011-05-11
Enrollment: 52
Sex: ALL
Minimum age (years): 4
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Free survival rate
timeFrame: 2 years after the start of the study
Secondary outcomes:
measure: To compare overall survival between the two treatment arms.
timeFrame: Follow-up of the last patient included up to the age of 20 years
measure: To compare the pattern of relapse between the two treatment arms
timeFrame: Follow-up of the last patient included up to the age of 20 years
measure: To explore the benefit and the risks of neurosurgery
timeFrame: Follow-up of the last patient included up to the age of 20 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut Curie
Study officials:
affiliation: Institut Curie
name: DOZ François, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.