Registrationsdatum der Studie
Einschluss der ersten teilnehmenden Person
Authorised-recruitment may be ongoing or finished
Paediatric Hepatic International Tumour Trial - PHITT
Interventional clinical trial of medicinal product
Design der Studie
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
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
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.
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.
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