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NCT01351870 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2025-09-15

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
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.
healthy Volunteers
false
maximum Age
22 Years
minimum Age
4 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. 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
    intervention Names
    1. Radiation: Standard Fractionation Regimen
    label
    Standard Fractionation Regimen
    type
    ACTIVE_COMPARATOR
  2. 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
    intervention Names
    1. Radiation: Hyperfractionated Radiotherapy
    label
    Hyperfractionated radiotherapy
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Standard Fractionation Regimen
    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
    name
    Standard Fractionation Regimen
    type
    RADIATION
  2. arm Group Labels
    1. Hyperfractionated radiotherapy
    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
    name
    Hyperfractionated Radiotherapy
    type
    RADIATION
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
52
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Free survival rate
    time Frame
    2 years after the start of the study
secondary Outcomes
  1. description
    Will hyperfractionated radiotherapy lead to a different progression free (PFS) and overall survival (OS) compared to the standard arm radiotherapy?
    measure
    To compare overall survival between the two treatment arms.
    time Frame
    Follow-up of the last patient included up to the age of 20 years
  2. description
    Will hyperfractionated RT lead to a different pattern of local tumour control/pattern of relapse with particular respect to local relapse (tumour bed, posterior fossa outside the tumour bed) compared to the standard arm RT? The time to local progression should be the measure for the local tumour control.
    measure
    To compare the pattern of relapse between the two treatment arms
    time Frame
    Follow-up of the last patient included up to the age of 20 years
  3. description
    To determine the toxicity of surgery.To investigate whether there are identifiable factors that correlate with toxicity. To define the impact of any complications of surgery on commencement of adjuvant therapy and on EFS.
    measure
    To explore the benefit and the risks of neurosurgery
    time Frame
    Follow-up of the last patient included up to the age of 20 years
Full study description
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.
Source references
references
  1. 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.
    pmid
    30392813
    type
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        toma patients (<a href="/clinicaltrials/NCT02724579">NCT02724579</a>), the molecular subgroup with the best prognosis.</p></li><li>The <a href="/clinicaltrials/NCT01351870">SIOP-PNET-4 (NCT01351870)</a> study compared daily radiation therapy (1.8 Gy fractions with 23.4 Gy to the neuraxis and a 30 Gy boost to the posterior fossa)
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        linicaltrials/NCT02724579">NCT02724579</a>), the molecular subgroup with the best prognosis.</p></li><li>The <a href="/clinicaltrials/NCT01351870">SIOP-PNET-4 (NCT01351870)</a> study compared daily radiation therapy (1.8 Gy fractions with 23.4 Gy to the neuraxis and a 30 Gy boost to the posterior fossa) with twice-per-day radiati
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    Preserved source evidence · Independent clinical review pending · Not medical advice