Study for children with medulloblastoma of standard risk, between 3-5 years old and less than 22 years old

• Conditions: Children with medulloblastoma of standard risk. Medulloblastoma is a highly cellular malignant embryonal neoplasm classified as a Primitive Neuro-ectodermal Tumour [PNET]; MedDRA version: 17.1Level: PTClassification code 10027107Term: MedulloblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-004868-30-FR
• Lead Sponsor: niversity Medical Center Hamburg-Eppendorf

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-07
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

a) Age at diagnosis, at least 3 - 5 years (depending on the country) and less than 22 years.

The date of diagnosis is the date on which first surgery/biopsy is undertaken.

b) Histologically proven medulloblastoma, including the following subtypes, as defined in the WHO classification (2007):
classic medulloblastoma desmoplastic/nodular medulloblastoma Pre-treatment central pathology review is considered mandatory.

c) Standard risk medulloblastoma, defined as:
- total or near total surgical resection with less than or equal to 1.5 cm2 (measured on axial plane) of residual
tumour on early postoperative MRI, without and with contrast, on central review;
- no CNS metastasis on MRI (cranial and spinal) on central review; )
- no tumour cells on the cytospin samples of lumbar CSF (see chapter 8.1.2. Post-operative Period, page 4,),
according to national regulations a CSF review might me required.
- no clinical evidence of extra-CNS metastasis.

In patients with significant residual tumor (> 1.5 cm2) after first surgery, secondary surgery should be considered. Patients whith a reduction of postoperative residual tumor through second surgery to less than or equal to 1.5 cm2 are eligible, if second surgery is performed within 14 days after first surgery.

d) Submission of high quality biological material including fresh frozen tumor samples for the molecular assessment of biological markers (such as the assessment of MYC gene copy number status) in national biological reference centers.

e) No amplification of MYC or MYCN (determined by FISH).

f) Treatment Arm - LR, low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by IHC (mandatory) and / or mutation analysis (optional).For PNET 5 MB - SR, average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional)
Treatment Arm- SR, average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional) .

g) No prior therapy for medulloblastoma other than surgery.

h) Radiotherapy aiming to start no more than 28 days after surgery. Failure to start radiotherapy within 40 days after surgery renders patients ineligible for the study.

i) CTC grades < 2 for liver, renal, and haematological function.

j) no significant sensineural hearing deficit as defined by pure tone audiomentry with bone conduction or air conduction and normal tympanogram shows no impairement = 20 dB at 1-3 kHz. If performance of pure tone audiometry is not possible postoperatively, normal otoacoustic emissions are acceptable, if there is no history of hearing deficit.

k) No medical contraindication to radiotherapy or chemotherapy, such as preexisting DNA breakage syndromes (e.g. Fanconi Anemia, Njimwegen breakage syndrome) Gorlin Syndrome or other reasons as defined by patient’s clinician;

l) No identified Turcot and Li Fraumeni syndrome.

m) Written informed consent (and patient assent where appropriate) for therapy according to the laws of each participating country.

n) National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).

Are the trial subjects under 18? yes
Number of subjects for this age range: 360
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for

Exclusion Criteria

a) One of the inclusion criteria is lacking.
b) Brainstem or supratentorial primitive neuro-ectodermal tumour.
c) Atypical teratoid rhabdoid tumour.
d) Medulloepithelioma.
e) Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), centrally confirmed.
f) Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or not determinable MYC or MYCN or ß-catenin.
g) Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF).
h) Patient previously treated for a brain tumour or any type of malignant disease.
i) DNA breakage syndromes (e.g. Fanconi anemia, Nijmegen breakage syndrome) or other, or identified Gorlin, Turcot, or Li Fraumeni syndrome.
j) Patients who are pregnant.
k) Female patients who are sexually active and not taking reliable contraception.
l) Patients who cannot be regularly followed up due to psychological, social, familial or geographic reasons.
m) Patients in whom non-compliance with toxicity management guidelines can be expected.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified