A significant proportion of HCC patients present with, or progress to, intermediate stage
disease and these patients are typically treated with transarterial chemo-embolisation (TACE)
or transarterial embolisation (TAE).
However, since TACE/TAE is generally a palliative therapy, it provides a potential backbone
for the addition of effective systemic therapies with the aim of improving survival outcomes.
Since TACE may liberate an abundance of tumour antigens and 'danger' signals, it may lend
itself to combination with immunotherapeutic strategies.
Nivolumab is a human monoclonal antibody. Nivolumab targets the programmed death-1 PD-1)
cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative
regulatory molecule expressed by activated T and B lymphocytes.
Inclusion Criteria:
1. Histological diagnosis of HCC and at least one uni-dimensional lesion measurable
according to RECIST 1.1 criteria by CT-scan or MRI.
2. Not a candidate for surgical resection or liver transplantation
3. Aged ≥16 years and estimated life expectancy >3 months
4. ECOG performance status 0-1
5. Adequate haematological function:
- Hb ≥9g/L
- Absolute neutrophil count ≥1.0x109/L
- Platelet count ≥60x109/L
6. Bilirubin ≤50 μmol/L, AST,ALT and ALP ≤5 x ULN
7. Adequate renal function; Creatinine ≤ 1.5ULN (Using Cockcroft-Gault Formula)
8. INR ≤1.6
9. Child-Pugh A (score ≤6) (Appendix D)
10. HAP score A, B or C (Appendix E)
11. No contra-indications to T-cell checkpoint inhibitor therapy (use of immunosuppressive
drugs including steroids at dose equivalent to prednisolone >10mg/day unless used as
replacement therapy; organ transplantation; subjects with an active, known or
suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism
only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, lichen planus or other conditions not
expected to recur in the absence of an external trigger are permitted to enrol).
12. Women of child-bearing potential should have a negative pregnancy test prior to study
entry. Both men and women must be using an adequate contraception method, which must
be continued for 5 months after completion of treatment for women and 7 months for men
13. Written informed consent
Exclusion Criteria:
1. Extrahepatic metastasis
2. Prior embolisation, systemic or radiation therapy for HCC
3. Any contraindications for hepatic embolisation procedures including portosystemic
shunt, hepatofugal blood flow, known severe atheromatosis
4. Investigational therapy or major surgery within 4 weeks of trial entry
5. History of variceal bleeding within the past 4 weeks
6. Child-Pugh cirrhosis B or C (score ≥7)
7. HAP score D
8. Hepatic encephalopathy
9. Ascites refractory to diuretic therapy
10. Documented occlusion of the hepatic artery or main portal vein5
11. Hypersensitivity to intravenous contrast agents
12. Active clinically serious infection > Grade 2 NCI-CTC
13. Pregnant or lactating women
14. Known history of HIV infection
15. HBV chronic infection with HBV DNA > 500IU/mL or without antiviral therapy; HBV
patients with cirrhosis should be treated.
17. History of second malignancy except those treated with curative intent more than three
years previously without relapse and non-melanotic skin cancer or cervical carcinoma in
situ 18. Evidence of severe or uncontrolled systemic disease, or laboratory finding that in
the view of the Investigator makes it undesirable for the patient to participate in the
trial 19. Psychiatric or other disorder likely to impact on informed consent 20. Patient is
unable and/or unwilling to comply with treatment and study instructions 20. Interstitial
lung disease that is symptomatic or may interfere with the detection or management of
suspected treatment-related pulmonary toxicity
21. Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial,
anti-viral or antifungal therapy within 7 days prior to administration of study medication
22. Positive test for latent TB or evidence of active TB
23. Hypersensitivity to any of the active substances or excipients
24. Patients who have received a live vaccine within 30 days prior to the first dose of
trial treatment
25. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of
the first dose of study drug administration
26. Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative
colitis
27. Participants with an active, known or suspected autoimmune disease. Participants with
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions
not expected to recur in the absence of an external trigger are permitted to enrol
