Clinical trial NCT03017326: Paediatric Hepatic International Tumour Trial
Official title: Paediatric Hepatic International Tumour Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatoblastoma
Carcinoma, Hepatocellular
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: Fundació Institut Germans Trias i Pujol
name: University Hospital Munich
name: University Hospital, Bonn
name: University of Kiel
name: University Hospital Tuebingen
name: University of Padova
name: Ludwig-Maximilians - University of Munich
name: Medical University of Gdansk
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Motol University Hospital
name: Rennes University Hospital
name: Children's University Hospital, Ireland
name: University of Oslo
name: Princess Maxima Center for Pediatric Oncology
name: Andaluz Health Service
name: Swiss Pediatric Oncology Group
name: Gothia Forum - Center for Clinical Trial
name: The Leeds Teaching Hospitals NHS Trust
name: Bambino Gesù Hospital and Research Institute
name: Newcastle University Centre for Cancer, Newcastle
name: Experimental Cancer Medicine Centres
name: XenTech, Evry
First posted: 2017-01-11
Enrollment: 450
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: From date of randomisation (or registration into the trial for non-randomised patients), until date of first failure event, assessed up to 6 years.
measure: Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria
timeFrame: From date of screening assessment until date of first response assessment, up to 63 days in Group F
Secondary outcomes:
measure: Failure-free survival (FFS)
timeFrame: 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.
measure: Overall survival (OS)
timeFrame: 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.
measure: Toxicity categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: From date of start of randomised treatment until date 30 days after last treatment.
measure: Chemotherapy-related cardiac, nephro- and oto-toxicity using Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: From date of start of randomised treatment until date 30 days after last treatment.
measure: Hearing loss according to the SIOP Boston Scale
timeFrame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
measure: Best Response
timeFrame: 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.
measure: Surgical resectability defined as complete resection, partial resection or transplant
timeFrame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
measure: Adherence to surgical guidelines
timeFrame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: St. Anna Kinderspital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Woluwe-Saint-Lambert
city: Prague
country: Czechia
facility: University Hospital Motol
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Rennes
country: France
facility: CHU de Rennes
city: Munich
country: Germany
facility: Ludwig-Maximillians-University Munich
city: Dublin
country: Ireland
facility: Children's Health Ireland Crumlin
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Utrecht
country: Netherlands
facility: Prinses Maxima Center
city: Nydalen
country: Norway
facility: Oslo University Hospital
city: Gdańsk
country: Poland
facility: Medical University of Gdansk
city: Córdoba
country: Spain
facility: University Hospital Reina Sofia
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Noah's Ark Children's Hospital for Wales
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Great North Children's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham Children's Hospital
city: Oxford
country: United Kingdom
facility: Oxford Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: University of Nottingham
name: Madhumita Dandapani, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Geneva
name: Marc Ansari, MD
role: PRINCIPAL_INVESTIGATOR
References: