International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma | Recruiting
International Society of Paediatric... | Recruiting
International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

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Medical Conditions
  • Brain Tumors
Primary Contact Details
Stefan Rutkowski, Prof. Dr. med.
58200 +49-40-7410
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
NCT02066220
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
The study PNET 5 MB has been designed for children with medulloblastoma of standard risk (according to the risk-group definitions which have been used so far; e.g. in PNET 4). With the advent of biological parameters for stratification into clinical medulloblastoma trials, the ß-catenin status will be the only criterion according to which study patients will be assigned to either treatment arm PNET 5 MB - LR or to PNET 5 MB - SR, respectively. The initial diagnostic assessments (imaging, staging, histology, and tumor biology) required for study entry are the same for both treatment arms.
Research Details
  • The aim of the LR-treatment arm is to confirm the high rate of event-free survival in patients between the ages of 3 to 5 years and less than 22, with 'standard risk' medulloblastoma with a low-risk biological profile. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by immuno-histochemistry (IHC). Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 18.0 Gy to the craniospinal axis. Following radiotherapy, patients will receive a reduced-intensity chemotherapy with a total of 6 cycles of chemotherapy consisting of 3 courses of cisplatin, CCNU and vincristine alternating with 3 courses of cyclophosphamide and vincristine.

    The aim of the SR-arm is to test whether concurrent carboplatin during radiotherapy followed by 8 cycles of maintenance chemotherapy in patients with 'standard risk' medulloblastoma with an average-risk biological profile may improve outcome. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC. Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 23.4 Gy to the craniospinal axis. Following radiotherapy, patients will receive a modified-intensity chemotherapy with a total of 8 cycles of chemotherapy consisting of 4 courses of cisplatin, CCNU and vincristine alternating with 4 courses of cyclophosphamide and vincristine.
Phase
Phase 2/Phase 3
Study Design
Sorry, this information is not available
Study Type
Interventional
Intervention
Radiation : Radiotherapy without Carboplatin, Drug : Reduced-intensity maintenance chemotherapy, Radiation : Radiotherapy with Carboplatin, Drug : Maintenance chemotherapy

Study Arm Groups : PNET 5 MB-LR (low-risk), PNET 5 MB-SR (standard-risk), PNET 5 MB-LR (low-risk), PNET 5 MB-SR (standard-risk), PNET 5 MB-SR (standard-risk)

Intervention Type
See Interventions above
Primary Outcome Measures
    3-year Event-Free Survival (EFS); LR-arm after 9 years, SR-arm after 105 events (approx. 10 years)
Secondary Outcome Measures
    Overall survival; 10 years; Pattern of relapse; 10 years; Late effects of therapy on endocrine function; 10 years; Late effects of therapy on audiology; 8 years; Late effects of therapy on neurology; 10 years; Late effects of therapy on quality of survival; 10 years; Progression-free survival; 10 years; Feasibility of carboplatin treatment; approx. 7 years; Residual tumor; 6 years; Leukoencephalopathy grading; 8 years
Publication(s)
Sorry, this information is not available
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
All
Age Range
3 Years - 21 Years
Who Can Participate
Patients
Number of Participants
360
Participant Inclusion Criteria
    Inclusion Criteria:

    1. Age at diagnosis, at least 3 - 5 years (depending on the country) and less than 22 years (LR-arm: less than 16 years). The date of diagnosis is the date on which surgery is undertaken.

    2. 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.

    3. 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 post-operative MRI, without and with contrast, on central review;

    - no central nervous system (CNS) metastasis on MRI (cranial and spinal) on central review;

    - no tumour cells on the cytospin of lumbar CSF

    - no clinical evidence of extra-CNS metastasis; Patients with a reduction of postoperative residual tumor through second surgery to less than or equal to 1.5 cm2 are eligible, if if timeline for start of radiotherapy can be kept.

    4. Submission of high quality biological material including fresh frozen tumor samples for the molecular assessment of biological markers (such as the assessment of myelocytomatosis oncogene (MYC) copy number status) in national biological reference centers. Submission of blood is mandatory for all patients, who agree on germline DNA studies. Submission of CSF is recommended.

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

    6. For LR-arm: 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).

    For SR-arm: average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional).

    7. No prior therapy for medulloblastoma other than surgery.

    8. 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.

    9. 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.

    10. Common toxicity criteria (CTC) grades < 2 for liver, renal, haematological function

    11. no significant sensorineural hearing deficit as defined by pure tone audiometry with bone conduction or air conduction and normal tympanogram showing no impairment ≥ 20 decibel (dB) at 1-3 kilohertz (kHz). If performance of pure tone audiometry is not possible postoperatively, normal otoacoustic emissions are acceptable, if there is no history for hearing deficit.

    12. 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.

    13. No identified Turcot and Li Fraumeni syndrome.

    14. 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.

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

    Exclusion Criteria:

    1. One of the inclusion criteria is lacking.

    2. Brainstem or supratentorial primitive neuro-ectodermal tumour.

    3. Atypical teratoid rhabdoid tumour.

    4. Medulloepithelioma; Ependymoblastoma

    5. Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), centrally confirmed.

    6. Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or MYC or MYCN or WNT subgroup status not determinable.

    7. Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF).

    8. Patient previously treated for a brain tumour or any type of malignant disease.

    9. DNA breakage syndromes (e.g. Fanconi anemia, Nijmegen breakage syndrome) or other, or identified Gorlin,Turcot, or Li Fraumeni syndrome.

    10. Patients who are pregnant.

    11. Female patients who are sexually active and not taking reliable contraception.

    12. Patients who cannot be regularly followed up due to psychological, social, familial or geographic reasons.

    13. Patients in whom non-compliance with toxicity management guidelines can be expected.
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
London
WC1N 3JH
Trial Contact(s)
Primary Trial Contact
Stefan Rutkowski, Prof. Dr. med.
58200 +49-40-7410
Other Trial Contacts
Katja von Hoff, Dr. med.
53394 +49-40-7410
Countries Recruiting
Austria, Belgium, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
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)
EudraCT Number
Not available for this trial
Funder(s)
  • Deutsche Kinderkrebsstiftung
Other Study ID Numbers
SIOP PNET 5 MB
Sponsor(s)
Universitätsklinikum Hamburg-Eppendorf
Key Dates

Recruitment Start Date

Jun 2014

Recruitment End Date

Apr 2024

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

07 Feb 2014

Date updated in source

05 May 2017