Paediatric Hepatic International Tumour Trial

Phase 1

• Conditions: Hepatoblastoma and Hepatocellular Carcinoma.; MedDRA version: 20.0Level: PTClassification code 10062001Term: HepatoblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 21.0Level: LLTClassification code 10019830Term: Hepatocellular carcinoma resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2016-002828-85-PL
• Lead Sponsor: Medical University of Gdansk

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-06
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

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/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

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/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

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/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

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/biochemistry:
o Absolute neutrophil count (ANC) >0.75 x 109/L
o Platelet count >75 x 109/L
o International normalised ratio(INR)/Prothrombin time (PT) <1.2x ULN for age-based local reference values
o K, Mg, Ca within normal range for age

Group E
At diagnosis:
• Patient has been diagnosed with HCC
• Tumour has been resected with negative margins
Group E1
• HCC secondary to underlying liver disease
Group E2
• HCC de novo, including fibrolamellar
• Adequate renal function determined by:
o Serum creatinine in t

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

Treatment Group Specific Exclusion Criteria
Group C:
• Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
Group D:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use with St John’s Wort which cannot be stopped prior to start of trial treatment
Group F:
• Peripheral Sensitive Neuropathy with functional impairment
• Personal or family history of congenital long QT syndrome
• QT/QTc interval >450msec for men and >470msec for women (corrected measurement of QT according to BAZETT formula)
• Patients who are unable to swallow tablets , where an oral solution is not available or approved

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified