Prospective Randomised Study of Doxorubicin in the Treatment of Hepatocellular Carcinoma by Drug-Eluting Bead Embolisation

Prospective Randomised Study of Doxorubicin in the Treatment of Hepatocellular Carcinoma by Drug-Eluting Bead Embolisation (PRECISION V)

The objective of this study is to assess the safety and efficacy of DC Bead™ delivered by intra-arterial embolisation for the treatment of Hepatocellular Carcinoma

Inclusion criteria

• Patients with a confirmed diagnosis of HCC according to the EASL criteria for diagnosis, see appendix 4 and staged according to the BCLC criteria.
• Patient chooses to participate and has signed the informed consent document
• Age above 18 years old
• Patients with HCC not suitable for resection or percutaneous ablation according to the BCLC Staging classification, see Figure 2.
• Patient is eligible for resection or percutaneous ablation but the treatment is unfeasible or the patient has declined. This decision must be documented in the patient's records.
• Patient is eligible for chemoembolisation prior to transplantation and the expected transplant waiting time exceeds 6 months.
• Patients who demonstrates recurrence following potentially curative treatment (resection and percutaneous ablation) who have clearly measurable disease according to RECIST or EASL
• Patients with Performance Status ECOG 0 and 1
• Patients with well preserved liver function (Child-Pugh A and B)
• Patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3 weeks.

Exclusion criteria

• Patients with another primary tumour, with the exception of conventional basal cell carcinoma or superficial bladder neoplasia

• Patients previously treated with transarterial embolisation (with or without chemotherapy).

• Patients previously treated with anthracyclines (ie doxorubicin).

• Patients' whose only measurable disease is within an area of the liver previously subjected to radiotherapy.

• Advanced liver disease:

  • Child-Pugh C,
  • active gastrointestinal bleeding,
  • encephalopathy or clinically relevant ascites.

• Bilirubin levels >3mg/dl

• Advanced tumoural disease:

  • BCLC class C, (vascular invasion including segmental portal obstruction, extrahepatic spread or cancer-related symptoms= ECOG 2, 3 and 4) or
  • BCLC class D (WHO performance status 3 or 4, Okuda III stage) or
  • Diffuse HCC defined as >50% tumour involvement of the whole liver

• Any contraindication for doxorubicin administration:

  • serum bilirubin >5mg/dL,
  • WBC <3000 cells/mm3
  • neutrophil <1500 cells/mm3,
  • cardiac ejection fraction <50 percent assessed by isotopic ventriculography, echocardiography or MRI

• Any contraindication for hepatic embolisation procedures:

  • porto-systemic shunt,
  • hepatofugal blood flow;
  • impaired clotting tests (platelet count <50000/mm3, prothrombin activity <50 percent),
  • renal insufficiency/failure, serum creatinine > 2mg/dl (177umol/l)
  • severe atheromatosis,
  • AST and/or ALT >5x ULN or, when greater >250U/l

• Women who are pregnant or breast feeding

• Allergy to contrast media

• Contraindication to hepatic artery catheterisation, such as severe peripheral vascular disease precluding catheterisation

• The availability of alternative therapies those, in the judgment of the physician (referring or treating), are more appropriate for the patient

• Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk, that would preclude the safe use of DC Bead™, or TACE

• Patients who are contraindicated for MRI