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SNCTP000002948 | EUCTR2016-002828-85 | BASEC2018-00859

Etude internationale sur les tumeurs hépatiques pédiatriques

Datenbasis: BASEC (Import vom 29.11.2021), WHO (Import vom 18.04.2021)
Geändert: 21.09.2021
Krankheitskategorie: Anderer Krebs

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

L’ Hépatoblastome (HB) et le carcinome hépatocellulaire (CHC) sont deux types de cancer du foie. Le cancer du foie est une maladie rare chez les enfants et les jeunes adultes et peut normalement être traité avec la chirurgie et la chimiothérapie (traitement médicamenteux). Cependant, une chimiothérapie peut mener à des effets secondaires au long cours. Le but de cette étude est de trouver des meilleures stratégies de traitement qui améliorent pas seulement le pronostic de la maladie, mais aussi la qualité de la vie du patient. Cette étude se propose d’évaluer l’efficacité d‘un traitement moins intense , dans le but de réduire les effets secondaires. Se propose en outre d'améliorer le pronostic des formes tumorales plus agressives, en comparant des nouvelles thérapies avec les stratégies actuelles.

Untersuchte Krankheiten (Datenquelle: BASEC)

L’hépatoblastome (HB) et le carcinome hépatocellulaire (CHC) chez les enfants, les adolescents et les jeunes adultes

Health conditions (Datenquelle: WHO)

Hepatoblastoma and Hepatocellular Carcinoma.
MedDRA version: 20.0Level: PTClassification code 10062001Term: HepatoblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: LLTClassification code 10019830Term: Hepatocellular carcinoma resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04]

Seltene Krankheit (Datenquelle: BASEC)

Ja

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

L'étude se compose de deux parties. Dans un prémier temps les patients subissent une chirurgie ou une biopsie où un prélèvement de la tumeur est récolté. Ces prélèvements sont ensuite envoyée à une équipe de spécialistes , qui travaillent au sein de cette étude afin de déterminer le type de la tumeur et comprendre ses caractéristiques. Selon les résultats de la première partie, les patients sont ensuite assignés dans les groupes de traitement différent. Dans chaque groupe, l'étude comparera deux ou trois stratégies de traitement différentes adaptées spécifiquement à ces patients. L'attribution sera aléatoire: un ordinateur décidera quel groupe de patients sera placé dans quel groupe. L'analyse des échantillons recueillies mènera aussi à une meilleure compréhension de la biologie de cancer de foie, qui aidera à découvrir de nouveaux médicaments et des thérapies pour les patients futurs.

Interventions (Datenquelle: WHO)


Trade Name: Cisplatin
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: 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: Doxorubicin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Doxorubicin hydrochloride
CAS Number: 25316-40-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Etoposide
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Etoposide
CAS Number: 33419-42-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Fluorouracil
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: Gemcitabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Gemcitabine
CAS Number: 95058-81-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Irinotecan
CAS Number: 97682-44-5
Other descriptive name: Campto
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Oxaliplatin
Pharmaceutical F

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

Diagnostic d'une tumeur de foie du type HB ou HCC
Patients moins de 30 ans

Ausschlusskriterien (Datenquelle: BASEC)

Traitement précédent avec des traitements de chimiothérapie/radiothérapie
Maladie récurrente
Infection incontrôlée
Tumeur secondaire
Grossesse ou allaitement

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
For Trial Entry:
• Clinical diagnosis of HB or histologically defined diagnosis of HB or HCC.
• Age =30 years
• Written informed consent for trial entry

For Allocation/Randomisation to Treatment Group:
All Groups
• Written Informed Consent for trial treatment participation
• Patient assessed as fit to receive group specific treatment
• For females of child-bearing potential, a negative pregnancy test prior to trial entry is required. Any patient who is of reproductive age must agree to use adequate contraception for the duration of the trial.

Group A (no treatment arm)
At diagnosis:
• Resected Tumour.
• Patient meets Very Low Risk definition according to CHIC guidelines.
Group A1 – No treatment arm
• Central pathology review confirming WDF histology.
Group A2- Treatment arm
• Central pathology review confirming non-WDF histology.
• Adequate renal function determined by:
o Serum creatinine in the normal range based on age appropriate local reference values or glomerular filtration rate (GFR) =60mL/min/1.73m2
• Adequate haematology/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

Group B
• Patient meets Low Risk definition according to CHIC Guidelines
• Adequate renal function determined by:
o Serum creatinine in the normal range based on age appropriate local reference values or glomerular filtration rate (GFR) =60mL/min/1.73m2
• Adequate haematology/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

Group C
• Patient meets Intermediate Risk definition according to CHIC Guidelines
• Adequate renal function determined by:
o Serum creatinine in the normal range based on age appropriate local reference values or glomerular filtration rate (GFR) =60mL/min/1.73m2
• Adequate cardiac function determined by:
o Shortening fraction =28% by local assessment method
o OR Ejection fraction =47% by local assessment method
• Adequate haematology/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

Group D
• Patient meets High Risk definition according to CHIC Guidelines
• Adequate renal function determined by:
o Serum creatinine in the normal range based on age appropriate local reference values or glomerular filtration rate (GFR) =60mL/min/1.73m2
• Adequate cardiac function determined by:
o Shortening fraction =28% by local assessment method
o OR Ejection fraction =47% by local assessment method
• Adequate haematology/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

Group E
At diagnosis:
• Patient has been diagnosed with HCC
• Tumour has been resected with negative margins
Group E1
• HCC secondary to underlying liver disease
Group E2
• HCC de novo, including fibrolamell
Exclusion criteria:
• Any previous chemotherapy or currently receiving anti-cancer agents
• Recurrent disease
• Previously received a solid organ transplant
• Uncontrolled infection
• Unable to follow the protocol for any reason
• Second malignancy
• Pregnant or breastfeeding women


Treatment Group Specific Exclusion Criteria
Group C:
• Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
Group D:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use with St John’s Wort which cannot be stopped prior to start of trial treatment
Group F:
• Peripheral Sensitive Neuropathy with functional impairment
• Personal or family history of congenital long QT syndrome
• QT/QTc interval >450msec for men and >470msec for women (corrected measurement of QT according to BAZETT formula)
• Patients who are unable to swallow tablets , where an oral solution is not available or approved

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002828-85

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2016-002828-85-IE

Weitere Informationen zur Studie

Registrationsdatum der Studie

20.06.2017

Einschluss der ersten teilnehmenden Person

20.09.2017

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

Paediatric Hepatic International Tumour Trial - PHITT

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: yesRandomised: yesOpen: yesSingle blind: noDouble blind: noParallel group: noCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: yesPlacebo: noOther: noNumber of treatment arms in the trial: 6

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Secondary Objective: - to report event free survival in all patient groups
- to evaluate prognostic factors, including the following:
> to provide a comprehensive and highly validated panel of diagnostic and prognostic biomarkers
> to determine if paediatric HCC is a biologically different entity to adult HCC
> to validate prospectively a clinical risk stratification
> to develop genomic and/or biomarker analysis to predict children who may have an increased risk of developing toxicity with chemotherapy
;Main Objective: - To evaluate if the outcome with 4 cycles of treatment is not inferior to the outcome with 6 cycles of treatment, for patients with Low Risk HB, resectable tumours.
- To compare outcome and toxicity in patients with Intermediate Risk HB, treated with one of three treatment regimens: C5VD (cisplatin/5-fluorouracil/vincristine/doxorubicin), SIOPEL-3 high risk (cisplatin, carboplatin and doxorubicin) and cisplatin monotherapy.
- To compare the outcomes in patients with High Risk HB with metastatic disease, treated with one of two post induction treatments (carboplatin and doxorubicin alternating with carboplatin and etoposide, carboplatin and doxorubicin alternating with vincristine and irinotecan)
- to determine whether the addition of gemcitabine and oxaliplatin (GEMOX) to cisplatin, doxorubicin and sorafenib improves outcome in unresectable HCC patients
- to collect biology in all HB and HCC patients;Timepoint(s) of evaluation of this end point: Evaluation of EFS will be until first failure event.
Evaluation of Response in HCC will be until end of treatment.;Primary end point(s): Event Free Survival (EFS) as defined as the time from randomisation (or registration into the trial for non-randomised patients) to the first failure event. Patients who have not had an event will be censored at their last follow-up date.
Failure events are:
•progression of existing disease or occurrence of disease at new sites,
•death from any cause prior to disease progression,
•diagnosis of a second malignant neoplasm.

Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria. The assessment will be performed after 3 cycles of PLADO, or 4 cycles of PLADO+S/GEMOx+S in Group F patients. Patients who are not assessable for response, e.g. because of early stopping of treatment or death, will be assumed to be non-responders.

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): Failure-Free Survival (FFS) is defined as per EFS (primary endpoint above) with the addition of failure to go to resection.
Overall Survival (OS) is defined as the time from randomisation (or registration for non-randomised patients) to death from any cause.
Toxicity will be recorded in relation to each cycle of randomised treatment and will be categorised and graded using Common Terminology Criteria for Adverse Events (CTCAE)
Chemotherapy-related cardiac, nephro- and oto- toxicity will be recorded in relation to each cycle of non-randomised treatment and will be categorised by CTCAE.
Hearing loss is defined as Grade 4 Boston grade oto-toxicity compared to baseline.
Best Response is defined as Complete Response (CR) or Partial Response (PR) and is defined in the protocol based on radiological (RECIST) response and AFP decline.Patients who are not assessable for response (e.g. because of early stopping of treatment or death) will be assumed to be non-responders.
Surgical resectability id defined as complete resection, partial resection or transplant following randomisation (or enrolement for non-randomised patients).
Adherence to surgical guidelines is defined as the local clinician's surgical decision to resect or not compared to the current SIOPEL surgical guidelines.;Timepoint(s) of evaluation of this end point: Evaluation of FFS will be until first failure event, including failure to resect.
Evaluation of OS and Best Response will be until the last follow up.
Evaluation of Toxicity and Chemotherapy-related toxicity will be until 30 days after End of Treatment.
Evaluation of Hearing Loss, Surgical resectability and Adherence to surgical guidelines will be until End of Treatment.

Kontakt für Auskünfte (Datenquelle: WHO)

European Commission

Ergebnisse der Studie (Datenquelle: WHO)

Zusammenfassung der Ergebnisse

Paediatric Hepatic International Tumour Trial

Link zu den Ergebnissen im Primärregister

noch keine Angaben verfügbar

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten

noch keine Angaben verfügbar

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Aarau, Basel, Bellinzona, Bern, Genf, Lausanne, Luzern, St Gallen, Zürich

Durchführungsländer (Datenquelle: WHO)

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

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Prof. Dr. med. Marc Ansari
+41 22 372 47 31
marc.ansari@hcuge.ch

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

David Law
Research Governance, University of Birmingham, Edgbaston
University of Birmingham
01214158011
researchgovernance@contacts.bham.ac.uk

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

David Law
Research Governance, University of Birmingham, Edgbaston
University of Birmingham
01214158011
researchgovernance@contacts.bham.ac.uk

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

University of Birmingham

Bewilligung durch Ethikkommission (Datenquelle: BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Commission Cantonale d’éthique de la recherche Genève (CCER)

Datum der Bewilligung durch die Ethikkommission

07.08.2018

Weitere Studienidentifikationsnummern

Studienidentifikationsnummer der Ethikkommission (BASEC-ID) (Datenquelle: BASEC)

2018-00859

Secondary ID (Datenquelle: WHO)

RG_15-114
NCT03017326
2016-002828-85-GB