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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Institut Curie
ClinicalTrials.gov Identifier:
NCT01351870
First received: May 9, 2011
Last updated: May 10, 2011
Last verified: January 2004
  Purpose

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.


Condition Intervention Phase
Medulloblastoma
Radiation: Standard Fractionation Regimen
Radiation: Hyperfractionated Radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomised Controlled Trial of Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma

Resource links provided by NLM:


Further study details as provided by Institut Curie:

Primary Outcome Measures:
  • Free survival rate [ Time Frame: 2 years after the start of the study ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 52
Study Start Date: April 2004
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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

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


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

Ages Eligible for Study:   4 Years to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01351870

Locations
France
Institut Curie
Paris, France, 75005
Sponsors and Collaborators
Institut Curie
Investigators
Principal Investigator: DOZ François, MD Institut Curie
  More Information

No publications provided

Responsible Party: Sylvie MARAL, Institut Curie
ClinicalTrials.gov Identifier: NCT01351870     History of Changes
Other Study ID Numbers: IC2003-06
Study First Received: May 9, 2011
Last Updated: May 10, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Medulloblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive

ClinicalTrials.gov processed this record on October 23, 2014