AN INTERNATIONAL PROSPECTIVE STUDY ON CLINICALLY STANDARD-RISK MEDULLOBLASTOMA IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH LOW-RISK BIOLOGICAL PROFILE (PNET 5 MB - LR) OR AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR)
- 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: 19.0Level: 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-CZ
- Lead Sponsor
- niversity Medical Center Hamburg-Eppendorf
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
LR-arm:
a) Age at diagnosis, at least 3 - 5 years (depending on the country) and less than 16 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
- no clinical evidence of extra-CNS metastasis.
Patients with a reduction of postoperative residual tumour through second surgery to less than or equal to 1.5 cm2 are eligible, if timeline for start of radiotherapy can be kept.
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. Submission of blood and CSF is mandatory for all patients, who agree on germline DNA studies. Submission of CSF is recommended.
e) No amplification of MYC or MYCN (determined by FISH).
f) Low-risk biological profile, defined as WNT subgroup positivity. The WNT subgroup is defined by the presence of (i) ß-catenin mutation (mandatory testing), or (ii) ß-catenin nuclear immuno-positivity by IHC (mandatory testing) and ß-catenin mutation, or (iii) ß-catenin nuclear immuno-positivity by IHC and monosomy 6 (optional testing).
g) No prior therapy for medulloblastoma other than surgery;
h) Radiotherapy aiming to start no more than 28 days after surgery. Foreseeable inability to start radiotherapy within 40 days after surgery renders patients ineligible for the study
i) Screening for the compliance with eligibility criteria should be completed, and patient should be included into the study within 28 days after first surgery (in case of second surgery within 35 days after first surgery). Inclusion of patients is not possible later than 40 days after first tumour surgery, or after start of radiotherapy.
j) CTC grades < 2 for liver, renal, haematological function
k) No significant sensineural hearing deficit as defined by pure tone audiomentry with bone conduction or air conduction and normal tympanogram showing 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 for hearing deficit.
l) No medical contraindication to radiotherapy or chemotherapy, such as preexisting DNA breakage syndromes (e.g. Fanconi Anemia, Nijmegen breakage syndrome), Gorlin Syndrome or other reasons as defined by patient’s clinician;
m) No identified Turcot and Li Fraumeni syndrome.
n) Written informed consent (and patient assent where appropriate) for therapy according to the laws of each participating country. Information must be provided to the patient on biological studies (tumour and germline), and written informed consent obtained of agreement for participation.
o) National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).
S
a) One of the inclusion criteria is lacking;
b) Brainstem or supratentorial primitive neuro-ectodermal tumour;
c) Atypical teratoid rhabdoid tumour;
d) Medulloepithelioma; Ependymoblastoma
e) Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), confirmed on central pathological review.
f) Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or WNT subgroup status not determinable.
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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method