Paediatric Hepatic International Tumour Trial (PHITT)

May 12, 2026 updated by: University of Birmingham

The PHITT trial is an over-arching study for patients with Hepatoblastoma (HB) and Hepatocellular Carcinoma (HCC). This trial will use a risk-adapted approach to the treatment of children diagnosed with HB.

Children with HCC will be included as a separate cohort.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The trial will evaluate whether reducing treatment for low risk HB patients maintains their excellent event free survival (EFS) and decreases acute and long-term toxicity. Intensification of therapy with the use of novel agents will be evaluated in the high risk group. The trial will also compare three different regimens in intermediate risk HB.

Patients with HCC will be divided into groups based on whether the tumour is resectable or unresectable and/or metastatic.

Evaluation of the biology of HB and HCC, using the identification/validation of novel and already reported prognostic biomarkers as well as toxicity biomarkers is a key strand of this trial, so patients in all risk groups can be registered. The trial is also designed to optimise the collection of clinically annotated biologic specimens and establish the world's largest repository of blood and tissue samples from paediatric patients with HB and HCC.

The trial includes 4 randomised comparisons addressing therapeutic questions. For low risk HB patients, outcome with a total of 4 cycles of treatment is not inferior to those receiving a total of 6 cycles of treatment.

For intermediate risk patients, 3 regimens will be compared for outcome and toxicity.

For high risk patients, 2 post induction regimens will be compared for outcome. For resected HCC patients, the addition of GEMOX to PLADO regimen will be compared.

In addition the following will be assessed:

  • To validate a new global risk stratification, defined by Children's Hepatic Tumours International Collaboration (CHIC)

  • To evaluate clinically relevant factors, including the following:

    • Provide a comprehensive and highly-validated panel of diagnostic and prognostic biomarkers
    • Determine if paediatric HCC is a biologically different entity to adult HCC
    • Develop genomic and/or biomarker analysis to predict children who may have an increased risk of developing toxicity with chemotherapy.
  • To establish a collection of clinically and pathologically-annotated biological samples.
  • Evaluate a surgical planning tool for an impact on decision making processes in POST-TEXT III and IV HB

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
450

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • St. Anna Kinderspital
  • Belgium
    • Woluwe-Saint-Lambert
      • Brussels, Woluwe-Saint-Lambert, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
  • Czechia
      • Prague, Czechia, 150 06 Prague 5
        • University Hospital Motol
  • Finland
      • Kuopio, Finland, FI20029 KYS
        • Kuopio University Hospital
  • France
      • Rennes, France, 35033
        • CHU de Rennes
  • Germany
      • Munich, Germany, 80337 Munich
        • Ludwig-Maximillians-University Munich
  • Ireland
      • Dublin, Ireland, 12 N512
        • Children's Health Ireland Crumlin
  • Israel
      • Petah Tikva, Israel, 4920235
        • Schneider Children's Medical Center
  • Netherlands
      • Utrecht, Netherlands, 3584 CS
        • Prinses Maxima Center
  • Norway
      • Nydalen, Norway, 0424 Oslo
        • Oslo University Hospital
  • Poland
      • Gdansk, Poland, 80-803
        • Medical University of Gdansk
  • Spain
      • Córdoba, Spain, 14004
        • University Hospital Reina Sofía
  • Switzerland
      • Geneva, Switzerland, CH 1211
        • Hôpitaux Universitaires de Genève
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZG
        • Royal Aberdeen Children's Hospital
      • Belfast, United Kingdom, BT12 6BE
        • Royal Belfast Hospital for Sick Children
      • Birmingham, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, United Kingdom, BS2 8BJ
        • Bristol Royal Hospital for Children
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital
      • Cardiff, United Kingdom, CF14 4XW
        • Noah's Ark Children's Hospital for Wales
      • Edinburgh, United Kingdom, EH9 1LW
        • Royal Hospital For Children
      • Glasgow, United Kingdom, G51 4TF
        • Royal Hospital For Children
      • Leeds, United Kingdom, LS1 3EX
        • Leeds General Infirmary
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Liverpool, United Kingdom, L12 2AP
        • Alder Hey Children's Hospital
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital
      • Manchester, United Kingdom, M13 9WL
        • Royal Manchester Children's Hospital
      • Newcastle upon Tyne, United Kingdom, NE1 4LP
        • Great North Children's Hospital
      • Nottingham, United Kingdom, NG7 2UH
        • Nottingham Children's Hospital
      • Oxford, United Kingdom, OX3 9DU
        • Oxford Children's Hospital
      • Sheffield, United Kingdom, S10 2TH
        • Sheffield Children's Hospital
      • Southampton, United Kingdom, SO16 6YD
        • University Hospital Southampton
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical diagnosis of HB* and histologically defined diagnosis of HB or HCC.

    *Histological confirmation of HB is required except in emergency situations where:

    • a) the patient meets all other eligibility criteria, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.
    • b) there is anatomic or mechanical compromise of critical organ function by tumour (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
    • c) Uncorrectable coagulopathy
  • Age ≤30 years
  • Written informed consent for trial entry

Exclusion Criteria:

  • Any previous chemotherapy or currently receiving anti-cancer agents
  • Recurrent disease
  • Previously received a solid organ transplant; other than orthotopic liver transplantation (OLT).
  • Uncontrolled infection
  • Unable to follow or comply with the protocol for any reason
  • Second malignancy
  • Pregnant or breastfeeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Group A Very Low Risk HB
Patients with well differentiated foetal histology will receive 2 cycles of Cisplatin (2x 100mg/m2). Patients will non-well differentiated histology will be followed up only (no intervention).
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Active Comparator: Group B Low Risk HB
Patients who are resected after 2 cycles of Cisplatin will be randomised to receive 4 or 6 cycles of Cisplatin overall (80mg/m2). Patients who are not resected will continue to receive up to 6 cycles of Cisplatin (80mg/m2) until resection.
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Active Comparator: Group C Intermediate Risk HB
Patients will be randomised to receive Cisplatin (80mg/m2), Carboplatin (500mg/m2) and Doxorubicin (60mg/m2) as SIOPEL-3HR (5 cycles), Cisplatin (100mg/m2), Doxorubicin (60mg/m2) 5-Fluorouracil (600mg/m2) and Vincristine (4.5mg/m2) as C5VD (6 cycles), or 6 cycles of high dose Cisplatin (100mg/m2)
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Drug: Doxorubicin
Arms C, D and E used in combination
Drug: Carboplatin
Arms C and D used in combination
Drug: 5Fluorouracil
Arm C used alone
Drug: Vincristine
Arms C and D used in combination
Active Comparator: Group D High Risk HB
Patients will receive SIOPEL-4 regimen (Cisplatin 70mg/m2, Doxorubicin 30mg/m2) then have surgery. Post surgery, patients with remaining metastases will be randomised to receive 6 cycles of either Carboplatin (500mg/m2) and Doxorubicin (40mg/m2) alternating with Carboplatin (800mg/m2) and Etoposide (400mg/m2), or Carboplatin (500mg/m2) and Doxorubicin (40mg/m2) alternating with Vincristine (3mg/m2) and Irinotecan (250mg/m2). Patients with no metastases will receive the standard treatment of 3 cycles of Carboplatin (500mg/m2) and Doxorubicin (40mg/m2).
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Drug: Doxorubicin
Arms C, D and E used in combination
Drug: Carboplatin
Arms C and D used in combination
Drug: Vincristine
Arms C and D used in combination
Drug: Etoposide
Arm D used in combination
Drug: Irinotecan
Arm D used in combination
Other: Group E Resected HCC
Patients with an underlying predisposition to HCC through genetic, viral or metabolic conditions will be followed up (no intervention). De novo or fibrolamellar HCC patients will receive 4 cycles of PLADO regimen (Cisplatin (80mg/m2) and Doxorubicin (60mg/m2)) over 4 cycles.
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Drug: Doxorubicin
Arms C, D and E used in combination
Active Comparator: Group F Unresected HCC
Patients will be randomised to receive up to 6 cycles of PLADO (Cisplatin 80mg/m2, Doxorubicin 60mg/m2) with Sorafenib (300mg/m2) or up to 8 cycles of PLADO with Sorafenib and GEMOX (Gemcitabine 1000mg/m2, Oxaliplatin 100mg/m2) with Sorafenib (300mg/m2)
Drug: Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
Drug: Doxorubicin
Arms C, D and E used in combination
Drug: Gemcitabine
Arm F used in combination
Drug: Oxaliplatin
Arm F used in combination
Drug: Sorafenib
Arm used in combination

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: From date of randomisation (or registration into the trial for non-randomised patients), until date of first failure event, assessed up to 6 years.

Event-free survival (EFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to 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.
From date of randomisation (or registration into the trial for non-randomised patients), until date of first failure event, assessed up to 6 years.
Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria
Time Frame: From date of screening assessment until date of first response assessment, up to 63 days in Group F
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 who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.
From date of screening assessment until date of first response assessment, up to 63 days in Group F

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Failure-free survival (FFS)
Time Frame: From date of randomisation (or registration into the trial for non-randomised patients) until date of first failure event, or date of last follow up assessment, assessed up to 6 years.

Failure-free survival (FFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to 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. failure to go to resection.
From date of randomisation (or registration into the trial for non-randomised patients) until date of first failure event, or date of last follow up assessment, assessed up to 6 years.
Overall survival (OS)
Time Frame: From date of randomisation (or registration for non-randomised patients) until date of death from any cause, or date of last follow up assessment, assessed up to 6 years.
Overall survival (OS) is defined as the time from randomisation (or registration for non-randomised patients) to death from any cause. Patients who have not died will be censored at their last follow-up date.
From date of randomisation (or registration for non-randomised patients) until date of death from any cause, or date of last follow up assessment, assessed up to 6 years.
Toxicity categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame: From date of start of randomised treatment until date 30 days after last treatment.
Toxicity will be recorded in relation to each cycle of randomised treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
From date of start of randomised treatment until date 30 days after last treatment.
Chemotherapy-related cardiac, nephro- and oto-toxicity using Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame: From date of start of randomised treatment until date 30 days after last treatment.
Chemotherapy-related cardiac, nephro- and oto-toxicity will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
From date of start of randomised treatment until date 30 days after last treatment.
Hearing loss according to the SIOP Boston Scale
Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Hearing loss will be measured according to the SIOP Boston Scale for oto-toxicity. The assessment will be performed at end of treatment (EOT) and follow up
From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Best Response
Time Frame: From date of first treatment until the date of last treatment, or until the date of first documented progression or date of death, assessed up to 6 months.
Best Response is defined as CR or PR and is based on radiological response (RECIST v1.1) and Alpha Fetoprotein (AFP) decline. Best Response will be measured throughout treatment period. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.
From date of first treatment until the date of last treatment, or until the date of first documented progression or date of death, assessed up to 6 months.
Surgical resectability defined as complete resection, partial resection or transplant
Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Surgical resectability is defined as complete resection, partial resection or transplant
From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Adherence to surgical guidelines
Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Adherence to surgical guidelines is defined as the local clinician's surgical decision to resect or not compared to the current SIOPEL surgical guidelines.
From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Birmingham

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Oslo
The Leeds Teaching Hospitals NHS Trust
University of Padova
Bambino Gesù Hospital and Research Institute
University of Kiel
Ludwig-Maximilians - University of Munich
University Hospital, Bonn
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Rennes University Hospital
Newcastle University
University Hospital Tuebingen
Andaluz Health Service
Fundació Institut Germans Trias i Pujol
Princess Maxima Center for Pediatric Oncology
Motol University Hospital
Medical University of Gdansk
University Hospital Munich
Children's University Hospital, Ireland
Gothia Forum - Center for Clinical Trial
Swiss Pediatric Oncology Group
Experimental Cancer Medicine Centres
XenTech, Evry

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Madhumita Dandapani, MD PhD, University of Nottingham
  • Principal Investigator: Marc Ansari, MD, University of Geneva, Switzerland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 24, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 14, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 10, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RG_15-114

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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