MedulloblastomaPhase 3SIOP-PNET-4NCT01351870
Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (PNET4)
A Phase 3 study testing Standard Fractionation Regimen and Hyperfractionated Radiotherapy in people with Medulloblastoma, run by Institut Curie at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 22 years
- Conditions the study is for
- Medulloblastoma
- What is being tested?
- Standard Fractionation Regimen and Hyperfractionated Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2004to Mar 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- One of the inclusion criteria is lacking.
- Brainstem or supratentorial primitive neuroectodermal tumour.
- Atypical teratoid rhabdoid tumour.
- Medulloepithelioma.
- Ependymoblastoma.
- Large cell médulloblastoma.
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Randomised Controlled Trial of Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
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.
Read the 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.
- Conditions
- Medulloblastoma
- Being tested
- Standard Fractionation Regimen, Hyperfractionated Radiotherapy
- Medical subject headings
- Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Fractionation RegimenRadiation
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
Hyperfractionated RadiotherapyRadiation
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Radiation: Hyperfractionated Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years after the start of the study
Secondary outcomes (3)
To compare overall survival between the two treatment arms.
Will hyperfractionated radiotherapy lead to a different progression free (PFS) and overall survival (OS) compared to the standard arm radiotherapy?
Measured: 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
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.
Measured: Follow-up of the last patient included up to the age of 20 years
To explore the benefit and the risks of neurosurgery
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.
Measured: Follow-up of the last patient included up to the age of 20 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2011 (estimated)
- Study startApr 2004
- Primary completionDec 2008
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MedulloblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- DOZ François, MD, Principal investigator, Institut Curie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01351870
- Sponsor's protocol ID
- IC2003-06
- Acronym
- SIOP-PNET-4
- Status last verified
- Sep 2025
- First submitted
- 9 May 2011
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
Publications
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.
PubMed 30392813
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomised Controlled Trial of Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
- ClinicalTrials.gov ID
- NCT01351870
- Acronym / sponsor ID
- SIOP-PNET-4 / IC2003-06
- Conditions
- Medulloblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Institut CurieUniversity, hospital or other
- Study start
- Apr 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 11 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Fractionation Regimen | Active comparator | Radiation: Standard Fractionation Regimen1.8 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 |
| Hyperfractionated radiotherapy | Experimental | Radiation: Hyperfractionated Radiotherapy1 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 |
Who may qualify
- Ages
- 4 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- One of the inclusion criteria is lacking.
- Brainstem or supratentorial primitive neuroectodermal tumour.
- Atypical teratoid rhabdoid tumour.
- Medulloepithelioma.
- Ependymoblastoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Fractionation Regimen1.8 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 Radiotherapy1 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 |
Primary outcome
Free survival rate
Time frame: 2 years after the start of the study
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.
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Derived from this study: PubMed 30392813Goschzik 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.
- Individual participant dataSharing planned: Yes. Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
DOZ François, MD principal investigator
Institut Curie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Standard Fractionation Regimen and Hyperfractionated Radiotherapy in people with Medulloblastoma, run by Institut Curie at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Free survival rate (time frame: 2 years after the start of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01351870, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.