Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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6 July 2020 |
Main ID: |
EUCTR2016-002828-85-BE |
Date of registration:
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07/05/2018 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Paediatric Hepatic International Tumour Trial
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Scientific title:
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Paediatric Hepatic International Tumour Trial - PHITT |
Date of first enrolment:
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29/11/2018 |
Target sample size:
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300 |
Recruitment status: |
Authorised-recruitment may be ongoing or finished |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002828-85 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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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: no Number of treatment arms in the trial: 6
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Austria
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Belgium
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Czech Republic
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France
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Germany
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Ireland
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Italy
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Netherlands
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Norway
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Poland
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Spain
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Sweden
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Switzerland
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United Kingdom
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Contacts
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Name:
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Sean Jennings
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Address:
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Research Governance, University of Birmingham, Edgbaston
B15 2TT
Birmingham
United Kingdom |
Telephone:
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01214158011 |
Email:
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researchgovernance@contacts.bham.ac.uk |
Affiliation:
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University of Birmingham |
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Name:
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Sean Jennings
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Address:
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Research Governance, University of Birmingham, Edgbaston
B15 2TT
Birmingham
United Kingdom |
Telephone:
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01214158011 |
Email:
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researchgovernance@contacts.bham.ac.uk |
Affiliation:
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University of Birmingham |
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Key inclusion & exclusion criteria
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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:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o Prothrombin time (PT) <1.2x ULN for age-based local reference values
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:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o Prothrombin time (PT) <1.2x ULN for age-based local reference values
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:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o Prothrombin time (PT) <1.2x ULN for age-based local reference values
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:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o Prothrombin time (PT) <1.2x ULN for age-based local reference values
Group E
• Patient has been diagnosed with HCC
• Tumour has been locally assessed as resectable
• 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:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o Prothrombin time (PT) <1.2x
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
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Hepatoblastoma and Hepatocellular Carcinoma. MedDRA version: 20.0
Level: PT
Classification code 10062001
Term: Hepatoblastoma
System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0
Level: LLT
Classification code 10019828
Term: Hepatocellular carcinoma non-resectable
System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0
Level: LLT
Classification code 10019830
Term: Hepatocellular carcinoma resectable
System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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Therapeutic area: Diseases [C] - Cancer [C04]
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Intervention(s)
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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
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Primary Outcome(s)
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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.
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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.
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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
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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
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Secondary Outcome(s)
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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.
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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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Secondary ID(s)
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NCT03017326
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RG_15-114
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ISRCTN17869351
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2016-002828-85-GB
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Source(s) of Monetary Support
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European Commission
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Ethics review
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Status: Approved
Approval date: 29/11/2018
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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