Paediatric Hepatic International Tumour Trial

NCT ID: NCT03017326

Last Updated: 2024-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

450 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-24

Study Completion Date

2027-08-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hepatoblastoma Carcinoma, Hepatocellular

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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).

Group Type OTHER

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

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.

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

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)

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

Doxorubicin

Intervention Type DRUG

Arms C, D and E used in combination

Carboplatin

Intervention Type DRUG

Arms C and D used in combination

5Fluorouracil

Intervention Type DRUG

Arm C used alone

Vincristine

Intervention Type DRUG

Arms C and D used in combination

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).

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

Doxorubicin

Intervention Type DRUG

Arms C, D and E used in combination

Carboplatin

Intervention Type DRUG

Arms C and D used in combination

Vincristine

Intervention Type DRUG

Arms C and D used in combination

Etoposide

Intervention Type DRUG

Arm D used in combination

Irinotecan

Intervention Type DRUG

Arm D used in combination

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.

Group Type OTHER

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

Doxorubicin

Intervention Type DRUG

Arms C, D and E used in combination

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)

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

Doxorubicin

Intervention Type DRUG

Arms C, D and E used in combination

Gemcitabine

Intervention Type DRUG

Arm F used in combination

Oxaliplatin

Intervention Type DRUG

Arm F used in combination

Sorafenib

Intervention Type DRUG

Arm used in combination

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cisplatin

Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination

Intervention Type DRUG

Doxorubicin

Arms C, D and E used in combination

Intervention Type DRUG

Carboplatin

Arms C and D used in combination

Intervention Type DRUG

5Fluorouracil

Arm C used alone

Intervention Type DRUG

Vincristine

Arms C and D used in combination

Intervention Type DRUG

Etoposide

Arm D used in combination

Intervention Type DRUG

Irinotecan

Arm D used in combination

Intervention Type DRUG

Gemcitabine

Arm F used in combination

Intervention Type DRUG

Oxaliplatin

Arm F used in combination

Intervention Type DRUG

Sorafenib

Arm used in combination

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Fundació Institut Germans Trias i Pujol

OTHER

Sponsor Role collaborator

University Hospital Munich

OTHER

Sponsor Role collaborator

University Hospital, Bonn

OTHER

Sponsor Role collaborator

University of Kiel

OTHER

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role collaborator

University of Padova

OTHER

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

Medical University of Gdansk

OTHER

Sponsor Role collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role collaborator

Motol University Hospital

OTHER

Sponsor Role collaborator

Rennes University Hospital

OTHER

Sponsor Role collaborator

Children's University Hospital, Ireland

OTHER

Sponsor Role collaborator

University of Oslo

OTHER

Sponsor Role collaborator

Princess Maxima Center for Pediatric Oncology

OTHER

Sponsor Role collaborator

Andaluz Health Service

OTHER_GOV

Sponsor Role collaborator

Swiss Pediatric Oncology Group

OTHER

Sponsor Role collaborator

Gothia Forum - Center for Clinical Trial

OTHER

Sponsor Role collaborator

The Leeds Teaching Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role collaborator

Newcastle University Centre for Cancer, Newcastle

UNKNOWN

Sponsor Role collaborator

Experimental Cancer Medicine Centres

OTHER

Sponsor Role collaborator

XenTech, Evry

UNKNOWN

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Madhumita Dandapani, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Marc Ansari, MD

Role: PRINCIPAL_INVESTIGATOR

University of Geneva

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

St. Anna Kinderspital

Vienna, , Austria

Site Status

Cliniques Universitaires Saint-Luc

Brussels, Woluwe-Saint-Lambert, Belgium

Site Status

University Hospital Motol

Prague, , Czechia

Site Status

Kuopio University Hospital

Kuopio, , Finland

Site Status

CHU de Rennes

Rennes, , France

Site Status

Ludwig-Maximillians-University Munich

Munich, , Germany

Site Status

Children's Health Ireland Crumlin

Dublin, , Ireland

Site Status

Schneider Children's Medical Center

Petah Tikva, , Israel

Site Status

Prinses Maxima Center

Utrecht, , Netherlands

Site Status

Oslo University Hospital

Nydalen, , Norway

Site Status

Medical University of Gdansk

Gdansk, , Poland

Site Status

University Hospital Reina Sofia

Córdoba, , Spain

Site Status

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

Site Status

Royal Aberdeen Children's Hospital

Aberdeen, , United Kingdom

Site Status

Royal Belfast Hospital for Sick Children

Belfast, , United Kingdom

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Noah's Ark Children's Hospital for Wales

Cardiff, , United Kingdom

Site Status

Royal Hospital for Children

Edinburgh, , United Kingdom

Site Status

Royal Hospital for Children

Glasgow, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Alder Hey Children's Hospital

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Great North Children's Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Nottingham Children's Hospital

Nottingham, , United Kingdom

Site Status

Oxford Children's Hospital

Oxford, , United Kingdom

Site Status

Sheffield Children's Hospital

Sheffield, , United Kingdom

Site Status

University Hospital Southampton

Southampton, , United Kingdom

Site Status

The Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Austria Belgium Czechia Finland France Germany Ireland Israel Netherlands Norway Poland Spain Switzerland United Kingdom

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RG_15-114

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.