Phase I Safety Study of Dendritic Cell Vaccine to Treat Patients With Hepatocellular Carcinoma

Patients diagnosed with hepatocellular carcinoma will get COMBIG-DC vaccinations at three occasions with 2-3 weeks and 3-5 weeks between vaccination 2 and 3 respectively. Adverse events will be registered until 6 months after last vaccination, as well as changes in vital signs (heart rate, blood pressure and body temperature) and lab parameters. Immunologic response will be evaluated by measuring immunologic markers in blood. The size of the tumor/tumors will be evaluated after 3 and 6 months and thereafter every three months until tumor progression.

For patients included after approval of Amendment 3 (2015-12-10), COMBIG-DC will be given as add on to standard treatment; sorafenib or Transarterial Chemoembolization (TACE).

Inclusion criteria

• Be informed of the nature of the study and have provided written informed consent
• At least 18 years of age.
• Diagnosis of hepatocellular carcinoma according to EASL criteria or pathology.
• Radiologically measurable liver tumor(s), i.e. at least 20 mm in longest uni-dimensional diameter as measured by CT/MRI
• Not eligible for curatively aiming treatment or TACE. Tumor stage B or C according to BCLC.
• For patients included according to Amendment 3: tumour stage A, B or C according to BCLC and

• eligible for sorafenib treatment or having ongoing sorafenib treatment for not more than 4 weeks ant the time for inclusion or
• eligible for TACE or having received not more than 1 previous TACE treatment.

Exclusion criteria

• Performance status > ECOG 2
• Liver function according to Child-Pugh >7 points.
• Known major reaction/adverse event in connection with previously made vaccination (e.g. asthma, anaphylaxia or other serious reaction).
• Known major reaction/adverse event in connection with previous transfusions of blood products
• Active autoimmune disease requiring treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases.
• Tested positive for HIV
• Active disease (HBV and HCV) requiring antiviral treatment
• Ongoing infection that requires treatment with antibiotics or antiviral medication
• Treatment with immunosuppressive treatments like corticosteroids (Immunosuppression (within 28 days) prior to the first injection of COMBIG-DC. Inhaled, intranasal and local steroids accepted), or mTor inhibitors within 28 days before first vaccination.
• Patients with prior history of malignancy other than HCC, within the preceding 3 years OR with relaps after complete response, except for 5 years follow-up of adequately treated in situ carcinoma without recurrences or non-melanoma skin cancer.
• Inadequate laboratory parameters, i.e.:

• P-Prothrombincomplex (PK) >1.4,
• Platelet count <50 75 x109/L
• Leukocyte count <3.0 x 109/L
• P-APT time outside normal limit
• Previous organ transplantation
• Women of Childbearing Potential (WOCBP) refusing to use adequate contraception (oral or injectable contraceptives, hormone releasing intrauterine device) throughout the study period.
• Pregnant or lactating women
• Life expectancy less than 3 months.
• Concomitant anti-tumor treatment (within 28 days) prior to the first injection of COMBIG-DC, except for sorafenib or TACE for patients included according to Amendment 3.
• For patients included according to Amendment 3: Previous systemic anti-cancer treatment.
• Investigational treatment (within 28 days) prior to the first injection of COMBIG-DC.
• Known blood dyscrasia (bleeding complication).
• Known malignancy in CNS
• Any reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.