Paediatric Hepatic International Tumour Trial

Carcinoma, Hepatocellular Clinical Trial

— PHITT  

Official title:

Paediatric Hepatic International Tumour Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03017326
• Other study ID #: RG_15-114
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 24, 2017
• Est. completion date: August 1, 2027

Study information

• Verified date: May 2024
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: August 1, 2027
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatoblastoma

Intervention

Drug:
• Cisplatin
Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
• Doxorubicin
Arms C, D and E used in combination
• Carboplatin
Arms C and D used in combination
• 5Fluorouracil
Arm C used alone
• Vincristine
Arms C and D used in combination
• Etoposide
Arm D used in combination
• Irinotecan
Arm D used in combination
• Gemcitabine
Arm F used in combination
• Oxaliplatin
Arm F used in combination
• Sorafenib
Arm used in combination

Locations

Country	Name	City	State
Austria	St. Anna Kinderspital	Vienna
Belgium	Cliniques Universitaires Saint-Luc	Brussels	Woluwe-Saint-Lambert
Czechia	University Hospital Motol	Prague
Finland	Kuopio University Hospital	Kuopio
France	CHU de Rennes	Rennes
Germany	Ludwig-Maximillians-University Munich	Munich
Ireland	Children's Health Ireland Crumlin	Dublin
Israel	Schneider Children's Medical Center	Petach Tikva
Netherlands	Prinses Maxima Center	Utrecht
Norway	Oslo University Hospital	Nydalen
Poland	Medical University of Gdansk	Gdansk
Spain	University Hospital Reina Sofia	Córdoba
Switzerland	Hopitaux Universitaires de Geneve	Geneva
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Noah's Ark Children's Hospital for Wales	Cardiff
United Kingdom	Royal Hospital for Children	Edinburgh
United Kingdom	Royal Hospital for Children	Glasgow
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Alder Hey Children's Hospital	Liverpool
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Great North Children's Hospital	Newcastle Upon Tyne
United Kingdom	Nottingham Children's Hospital	Nottingham
United Kingdom	Oxford Children's Hospital	Oxford
United Kingdom	Sheffield Children's Hospital	Sheffield
United Kingdom	University Hospital Southampton	Southampton
United Kingdom	The Royal Marsden Hospital	Sutton

Sponsors (23)

Lead Sponsor

Collaborator

University of Birmingham

Andaluz Health Service, Bambino Gesù Hospital and Research Institute, Children's University Hospital, Ireland, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Experimental Cancer Medicine Centres, Fundació Institut Germans Trias i Pujol, Gothia Forum - Center for Clinical Trial, Ludwig-Maximilians - University of Munich, Medical University of Gdansk, Motol University Hospital, Prague, Newcastle University Centre for Cancer, Newcastle, Princess Maxima Center for Pediatric Oncology, Rennes University Hospital, Swiss Pediatric Oncology Group, The Leeds Teaching Hospitals NHS Trust, University Hospital Munich, University Hospital Tuebingen, University Hospital, Bonn, University of Kiel, University of Oslo, University of Padova, XenTech, Evry

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS)	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.
Primary	Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria	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	Failure-free survival (FFS)	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.
Secondary	Overall survival (OS)	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.
Secondary	Toxicity categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)	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.
Secondary	Chemotherapy-related cardiac, nephro- and oto-toxicity using Common Terminology Criteria for Adverse Events (CTCAE)	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.
Secondary	Hearing loss according to the SIOP Boston Scale	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.
Secondary	Best Response	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.
Secondary	Surgical resectability defined as complete resection, partial resection or transplant	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.
Secondary	Adherence to surgical guidelines	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.