Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)
Das Medulloblastom ist ein bösartiger Hirntumor. Die Therapie besteht aus einer Kombination von Operation, Strahlentherapie und Chemotherapie. Es besteht die Notwendigkeit, die Behandlungsergebnisse von Patienten mit Hochrisiko-Medulloblastom (HR-MB) zu verbessern und die kurz- und langfristigen Nebenwirkungen der Behandlung zu minimieren. Zu HR-MB gehören Medulloblastome gewisser biologischer Untergruppen und Medulloblastome mit Metastasen. In verschiedenen Ländern und verschiedenen Kliniken gibt es unterschiedliche anerkannte Therapiestrategien. Diese umfassen verschiedene Strahlentherapieschemen und verschiedene Chemotherapieschemen. Es ist noch nicht bekannt, welche(s) dieser Therapieoption(en) die beste(n) ist/sind. Dies soll in dieser Studie durch einen direkten Vergleich herausgefunden werden.
Malattie studiate(Fonte di dati: BASEC)
Medulloblastom
Health conditions
(Fonte di dati: WHO)
Histologically proven high-risk medulloblastoma, with any of the currently defined histological subtypes. High-risk disease is defined as patients with sonic hedgehog (SHH) subgroup or non-SHH/non-wingless-type (WNT) (Groups 3 and 4) medulloblastoma, with at least one additional high risk feature
MedDRA version: 20.0Level: PTClassification code 10027107Term: MedulloblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04]
Malattia rara
(Fonte di dati: BASEC)
No
Interventi esaminati (p. es. medicamento, terapia, campagna)
(Fonte di dati: BASEC)
Nach der Tumoroperation und einer ersten Chemotherapie werden die Patientinnen und Patienten durch Zufallsprinzip entweder mit einem konventionellen Strahlentherapieschema (1x pro Tag) oder einem hyperfraktionierten Schema (2x pro Tag) oder einer Hochdosis-Chemotherapie gefolgt von einem konventionellen Strahlentherapieschema behandelt. Die Strahlentherapie beginnt ungefähr 3–4 Wochen nach der Induktionschemotherapie oder 6 Wochen nach der hochdosierten Chemotherapie. Patientinnen und Patienten, welche zur ersten oder zweiten Gruppe gehören, werden anschliessend durch Zufallsprinzip eingeteilt für zwei verschiedene Erhaltungschemotherapieschemen (Cisplatin/Lomustin/Vincristin/Cyclophosphamid oder Temozolomid). Patientinnen und Patienten der dritten Gruppe erhalten alle dieselbe Erhaltungstherapie (Temozolomid). Durch Verlaufskontrollen wird überprüft, welches Schema die beste Wirkung zeigt bezüglich Tumorkontrolle (Heilungsraten) und bezüglich Langzeitnebenwirkungen der Therapie. Die Behandlung des HR-MB dauert in der Regel ungefähr 12 Monate. (Dauer der einzelnen Therapieelemente: erste Chemotherapie: 6 Wochen, davon an 2 x 5 Tagen ambulante Chemotherapieinfusionen; konventionelle Strahlentherapie: 6 Wochen 1x täglich jeweils an 5 Tagen pro Woche, hyperfraktionierte Strahlentherapie: knapp 5 Wochen 2x täglich jeweils an 5 Tagen pro Woche; Hochdosischemotherapie: ca. 2 x 3 Wochen; Erhaltungstherapie mit Cisplatin/Lomustin/Vincristin/Cyclophosphamid: ca. 9 Monate, davon 8 Hospitalisationen zu je 2-3 Tagen und 8 ambulante Chemotherapiegaben, Erhaltungschemotherapie mit Temozolomid: ca. 6 Monate, davon jeweils ca. 2x pro Monat ein ambulanter Arztbesuch). Vor, während und nach der Strahlen- und Chemotherapie sowie während des Nachbeobachtungszeitraums, werden die neurologischen, neuropsychometrischen und kognitiven Fähigkeiten der Patientinnen und Patienten beurteilt. Sie werden auch gebeten Fragebögen auszufüllen (bei den Visiten, 2 bzw. 5 Jahre nach der Diagnose, sowie nach Vollendung des 18. Lebensjahres). Dabei handelt es sich um mehrere kurze Fragebögen, die online in einem interaktiven Computerprogramm ausgefüllt werden können. Verglichen mit einer Therapie ausserhalb einer Studie nach bisherigen Therapieschemen entstehen durch die Teilnahme an dieser Studie keine zusätzlichen Arztbesuche oder Hospitalisationen.
Interventions
(Fonte di dati: WHO)
Product Name: Thiotepa
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Thiotepa
CAS Number: 52-24-4
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 15-100
Product Name: Vincristine
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Vincristine
CAS Number: 57-22-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 500-2000
Product Name: Temozolomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
CAS Number: 85622-93-1
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-250
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: carboplatin
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
CAS Number: 15663-27-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Product Name: Lomustine
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lomustine
CAS Number: 13010-47-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Criteri per la partecipazione alla sperimentazione
(Fonte di dati: BASEC)
• Neu diagnostiziertes high-risk Medulloblastom
• Keine vorherige Behandlung des Medulloblastoms, ausser Vorgängiger Operation oder einem Behandlungszyklus mit den Chemotherapien Carboplatin und Etoposid
• Patienten zwischen 3 und 18 Jahren am Tag der Diagnose
Criteri di esclusione
(Fonte di dati: BASEC)
• Patienten mit bestimmten Keimbahngenveränderungen (bestimmte Tumorprädispositionserkrankungen)
• Tumoren ohne biologische Hochrisikofaktoren
• Patientinnen, die schwanger sind oder stillen
Inclusion/Exclusion Criteria
(Fonte di dati: WHO)
Gender:
Female: yes
Male: yes
Inclusion criteria:
Inclusion criteria for trial entry and R1
?Histologically proven (centrally reviewed) high-risk medulloblastoma, with any of the currently defined histological subtypes. High-risk disease is defined as patients with sonic hedgehog (SHH) subgroup or non-SHH/non-wingless-type (WNT) (Groups 3 and 4) medulloblastoma, with at least one of the following high risk features:
oMetastatic disease: Chang Stage M1, M2 and M3.
oLarge cell/Anaplastic MB (as defined by World Health Organisation (WHO) criteria 2016
oPatients with significant residual tumour (> 1.5 cm2) following surgical resection of the primary tumour and other biological risk factors
oPatients with MYC or MYCN amplified tumours (unless MYCN amplified Group 4 without any other high risk factors)
oPatients with SHH subgroup tumours harbouring somatic TP53 mutations.
?Age at diagnosis =3 years. The date of diagnosis is the date on which initial surgery is undertaken.
?Submission of biological material, including fresh frozen tumour samples and blood, in accordance with national and international schemes for molecular assessment of biological markers, and for associated biological studies.
?No prior treatment for medulloblastoma, other than surgery, with the exception of one cycle of induction chemotherapy with carboplatin and etoposide may be given prior to trial entry and randomisation where there is clinical urgency to start treatment
?Adequate hepatic function defined as:
oTotal bilirubin = 1.5 times upper limit of normal (ULN) for age, unless the patient is known to have Gilbert?s syndrome
oALT or AST < 2.5 X ULN for age
?Adequate renal function defined as creatinine < 1.5 x ULN
?Adequate haematological function defined as ANC =1 x 109/L; platelets = 100 x 109/L
?No significant hearing deficit in at least one ear (significant hearing deficit defined as Chang grade 3 or above)
?Medically fit to receive protocol treatment
?Documented negative pregnancy test for female patients of childbearing potential
?Patient agrees to use effective contraception whilst on treatment (patients of childbearing potential)
?Written informed consent from the patient and/or parent/legal guardian
Inclusion criteria for Randomisation 2 (R2)
?Patient entered into the SIOP-HRMB trial at diagnosis
?Patient treated with:
oEither Arm A (conventional radiotherapy) or Arm B (HART) as part of R1
Are the trial subjects under 18? yes
Number of subjects for this age range: 750
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 99
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
Exclusion criteria:
Exclusion criteria for trial entry and randomisation 1:
?Patients with proven or with high likelihood of Germline TP53, APC, PTCH, SUFU, PALB2, BRCA2 gene alteration or any other DNA repair defect.
?Group 4 patients with MYCN amplification and no other high-risk factor
?Patients with ?-catenin mutation positive WNT medulloblastoma irrespective of other risk factors
?Patients with significant residual tumour (> 1.5 cm2) following surgical resection of the primary tumour and no other biological risk factors.
?Chang Stage M4 disease
?Brainstem or embryonal tumours in other sites
?Patients previously treated for a brain tumour or any type of malignant disease
?Medical contraindication to radiotherapy or chemotherapy
?Known hypersensitivity to any of the treatments or excipients
?Females who are pregnant or breastfeeding
?Patients who cannot be regularly followed up due to psychological, social, family, geographical or other issues
?Patients for whom non-compliance with treatment, management guidelines or monitoring is expected.
-
Altre informazioni sulla sperimentazione
Data di registrazione della sperimentazione
12 gen 2023
Stato di reclutamento
NA
Titolo scientifico
(Fonte di dati: WHO)
An International Prospective Trial on High-Risk Medulloblastoma in Patients Older than 3 Years - SIOP-HRMB
Tipo di sperimentazione
(Fonte di dati: WHO)
Interventional clinical trial of medicinal product
Disegno della sperimentazione
(Fonte di dati: WHO)
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Radiotherapy Number of treatment arms in the trial: 5
Fase
(Fonte di dati: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Punti finali primari
(Fonte di dati: WHO)
Main Objective: ?To evaluate whether outcome in children, young people and adults with high risk medulloblastoma (HR-MB) is improved over standard therapy for those treated with;(i) conventional (once a day) radiotherapy(ii) hyperfractionated-accelerated radiotherapy (HART), or (iii) high dose chemotherapy with thiotepa followed by conventional radiotherapy.
?To evaluate whether outcome in HR-MB is different for those treated with two different maintenance chemotherapy therapies (standard four-drug combination given as 8 cycles, alternating between cisplatin, lomustine and vincristine; and cyclophosphamide and vincristine; vs single agent oral temozolomide over 6 cycles)
;Secondary Objective: ?To study the late effects of treatment and their impact on quality of survival (QoS), including neurocognitive function, neurological impairment, endocrine impairment, audiological function, and secondary tumours.
?To conduct comprehensive prospective biological studies in HR-MB, with the aims of (i) understanding the biological basis of HR-MB, (ii) identification and validation of diagnostic and prognostic biomarkers, and (iii) identification and validation of molecular targets with therapeutic potential and associated predictive biomarkers.
?To conduct prospective QoS, toxicity and pharmacogenomic studies with the aim of exploring clinical, host and tumour factors, and genetic variants, that relate to early and late side-effects of treatment and survival parameters.
;Primary end point(s): The primary outcome measure is event-free survival (EFS).
An ?event? is considered to be any progression or relapse of disease, any deaths, and any occurrence of a secondary neoplasm.
?Relapse? is defined as the appearance of local disease, metastasis, or both following documented complete resection, or previous complete response.
?Progression? is defined as tumour growth > 25% (based on the three-dimensional measurement on the MRI) in the case of residual tumour.
?Secondary neoplasm? is defined as any diagnosed neoplasm that was distinct from medulloblastoma.
;Timepoint(s) of evaluation of this end point: Event Free Survival is defined as the time from the date of randomisation for each randomised question respectively to the date of the event; patients will be censored at date last seen if lost to follow-up.
Punti finali secondari
(Fonte di dati: WHO)
Secondary end point(s): Overall survival (OS) and progression-free survival (PFS) are secondary outcome measures.
Pattern of relapse
Indirect and direct measures of Quality of Survival (QoS)
Audiological toxicity
Endocrine function
Neurological function
Biological tumour markers;Timepoint(s) of evaluation of this end point: Overall survival and progression free survival are defined as the time from the date of randomisation to the date of death, relapse or progression for PFS or to date of death for OS; patients will be censored at date last seen if lost to follow-up.
Pattern of relapse is defined as the time from the date of surgery and ends on the date of appearance of relapse/progression
Indirect and direct measures of Quality of Survival will be assessed throughout the trial.
Audiological toxicity, Endocrine function and Neurological function will be assessed throughout the trial.
Biological tumour markers will be evaluated from pre-treatment samples.
Contatto per informazioni
(Fonte di dati: WHO)
Cancer Research UK;Deutsche Kinderkrebsstiftung
Risultati della sperimentazione
(Fonte di dati: WHO)
Sintesi dei risultati
An International Prospective Trial on High-Risk Medulloblastoma in Patients Older than 3 Years
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, Finland, France, Germany, Ireland, Italy, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom
Contatto per maggiori informazioni sulla sperimentazione
Dati della persona di contatto in Svizzera
(Fonte di dati: BASEC)
PD Dr. med. Nicolas Gerber
+41 44 266 74 55
nicolas.gerber@kispi.uzh.ch
Contatto per informazioni generali
(Fonte di dati: WHO)
Eileen Grimes
CRCTU, School of Cancer Sciences, Vincent Drive
University of Birmingham
01214147581
siop-hrmb@trials.bham.ac.uk
Contatto per informazioni scientifiche
(Fonte di dati: WHO)
Eileen Grimes
CRCTU, School of Cancer Sciences, Vincent Drive
University of Birmingham
01214147581
siop-hrmb@trials.bham.ac.uk
Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)
Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)
Kantonale
Ethikkommission Zürich
Data di autorizzazione da parte della commissione d’etica
19.10.2021
Altri numeri di identificazione delle sperimentazioni
Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID)
(Fonte di dati: BASEC)
2021-01423
Secondary ID (Fonte di dati: WHO)
RG18205BN3010
ISRCTN16314648
2018-004250-17-GB
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