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SNCTP000001204 | NCT02066220

Therapieoptimierungsstudie und Register für Kinder/Jugendliche/junge Erwachsene älter als 3 bis 5 Jahre mit Standardrisiko-Medulloblastom

Base di dati: BASEC (Importata da 27.01.2022), WHO (Importata da 18.01.2022)
Cambiato: 31.07.2019
Categoria di malattie: Malattie del sistema nervoso, Altro cancro

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Wir führen die Studie SIOP PNET 5-Medulloblastoma (SIOP PNET 5-MB) durch, um die Heilungschancen von Kindern, Jugendlichen und jungen Erwachsenen mit Medulloblastomen - bösartigen Hirntumoren - weiter zu verbessern und gleichzeitig die während und nach der Therapie auftretenden Nebenwirkungen zu minimieren. Potentielle Studienteilnehmer haben ein Alter zwischen 3 und 22 Jahren und sind an einem Medulloblastom erkrankt. Studienunabhängig wird der Tumor operativ so vollständig wie möglich entfernt. Das Resultat der Operation, die Verbreitung der Krebszellen im Körper und der Gesundheitszustand des Patienten werden anschliessend durch invasive und nicht-invasive Methoden geprüft. Bei potentiellen Studienteilnehmern werden weitere biologische Analysen des Tumorgewebes sowie Keimbahnuntersuchungen (Erbgutuntersuchungen) vorgenommen. Die Teilnehmer werden je nach biologischen Eigenschaften des Tumors und Resultat der Keimbahnuntersuchung in vier verschiedene Behandlungsgruppen eingeteilt. Während der folgenden Bestrahlung bekommt die Hälfte der Patienten mit einem durchschnittlichen biologischen Profil das Chemotherapiemedikament Carboplatin verabreicht. Die Auswahl erfolgt per Zufall. Alle Studienteilnehmer erhalten im Anschluss an die Bestrahlung eine Chemotherapie mit weiteren Chemotherapiemedikamenten, deren Zusammenstellung basierend auf den Erkenntnissen verschiedener Vorgängerstudie leicht abgeändert wurde. Patienten mit einem günstigen Krankheitsprofil bekommen eine Strahlentherapie und eine Chemotherapie in reduzierter Dosis. Patienten mit weiteren Krankheitsprofilen bekommen Kombinationen von Strahlentherapie und Chemotherapiemedikamenten, welche ebenfalls an ihr Profil angepasst werden. Patienten mit bestimmten krebsverursachenden Keimbahnveränderungen können in den Registerarm dieser Studie eingeschlossen werden.

Malattie studiate (Fonte di dati: BASEC)

Standardrisiko-Medulloblastom

Health conditions (Fonte di dati: WHO)

Brain Tumors

Malattia rara (Fonte di dati: BASEC)

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: BASEC)

Chemotherapie (Carboplatin, Cisplatin, Lomustin, Vincristin, Cyclophosphamid, Doxorubicin, Methotrexat, Vinblastin)

Interventions (Fonte di dati: WHO)

Radiation: Radiotherapy without Carboplatin;Drug: Reduced-intensity maintenance chemotherapy;Radiation: Radiotherapy with Carboplatin;Drug: Maintenance chemotherapy

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

• Alter: Kinder und Jugendliche im Alter von mindestens 3-5 Jahren (3 Jahre bei klassischem Medulloblastom und 5 Jahre bei desmoplastischem/nodulärem Medulloblastom)
• Histologisch bestätigtes Medulloblastom inklusive Subtypen: klassisches Medulloblastom und desmoplastisches/noduläres Medulloblastom
• Einwilligung in Keimbahnuntersuchungen und Einsendung einer Blutprobe
• U.a.

Criteri di esclusione (Fonte di dati: BASEC)

• Mindestens eines der Einschlusskriterien ist fehlend
• Gewisse Erkrankungskonstellationen (z.B. Metastasen oder grosser Tumorrest nach der Operation ohne bestimmte biologische Eigenschaft, anaplastisches/grosszelliges Medulloblastom u.a.)
• Patient ist schwanger
• U.a.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


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.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT02066220

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02066220

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

07.02.2014

Inserimento del primo partecipante

01.06.2014

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

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)

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional

Disegno della sperimentazione (Fonte di dati: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Fase (Fonte di dati: WHO)

Phase 2/Phase 3

Punti finali primari (Fonte di dati: WHO)

3-year Event-Free Survival (EFS)

Punti finali secondari (Fonte di dati: WHO)

Overall survival;Pattern of relapse;Late effects of therapy on endocrine function;Late effects of therapy on audiology;Late effects of therapy on neurology;Late effects of therapy on quality of survival;Progression-free survival;Feasibility of carboplatin treatment;Residual tumor;Leukoencephalopathy grading

Contatto per informazioni (Fonte di dati: WHO)

Please refer to primary and secondary sponsors

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Aarau, Basilea, Bellinzona, Berna, Ginevra, Losanna, Luzern, San Gallo, Zurigo

Paesi di esecuzione (Fonte di dati: WHO)

Austria, Belgium, Czech Republic, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

Dr. med. Nicolas Gerber
+41 44 266 74 55
nicolas.gerber@kispi.uzh.ch

Contatto per informazioni generali (Fonte di dati: WHO)

Francois Doz, Prof. Dr.;Stefan Rutkowski, Prof. Dr. med.
Institut Curie Paris, France
+49-40-7410
r.rutkowski@uke.de

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Francois Doz, Prof. Dr.;Stefan Rutkowski, Prof. Dr. med.
Institut Curie Paris, France
+49-40-7410
r.rutkowski@uke.de

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Universitätsklinikum Hamburg-Eppendorf

Altri sponsor (Fonte di dati: WHO)

Deutsche Kinderkrebsstiftung

Altri numeri di identificazione delle sperimentazioni

Secondary ID (Fonte di dati: WHO)

2011-004868-30
SIOP PNET 5 MB