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

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ClinicalTrials.gov Identifier: NCT01351870
Recruitment Status : Active, not recruiting
First Posted : May 11, 2011
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
Institut Curie

Tracking Information
First Submitted Date  ICMJE May 9, 2011
First Posted Date  ICMJE May 11, 2011
Last Update Posted Date February 12, 2020
Study Start Date  ICMJE April 2004
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2011)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2011)
  • 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 ]
    Will hyperfractionated radiotherapy lead to a different progression free (PFS) and overall survival (OS) compared to the standard arm radiotherapy?
  • 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 ]
    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.
  • 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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
Official Title  ICMJE A Prospective Randomised Controlled Trial of Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Medulloblastoma
Intervention  ICMJE
  • Radiation: Standard Fractionation Regimen

    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: Hyperfractionated Radiotherapy

    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 Arms  ICMJE
  • Active Comparator: Standard Fractionation Regimen

    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: Radiation: Standard Fractionation Regimen
  • Experimental: Hyperfractionated radiotherapy

    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: Radiation: Hyperfractionated Radiotherapy
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 10, 2011)
52
Original Actual Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 22 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01351870
Other Study ID Numbers  ICMJE IC2003-06 PNET4
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut Curie
Study Sponsor  ICMJE Institut Curie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: DOZ François, MD Institut Curie
PRS Account Institut Curie
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP