Trade Name: Cisplatin
Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Cisplatin
CAS Number: 15663-27-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Doxorubicin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Doxorubicin hydrochloride
CAS Number: 25316-40-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Etoposide
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Etoposide
CAS Number: 33419-42-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Fluorouracil
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: Gemcitabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Gemcitabine
CAS Number: 95058-81-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Irinotecan
CAS Number: 97682-44-5
Other descriptive name: Campto
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Oxaliplatin
Pharmaceutical F

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 fibrolamell
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