A Phase I Open-label Study to Evaluate Safety and Immunologic Response of COMBIG-DC Administered Intra-tumorally in Patients With Hepatocellular Carcinoma
A Phase I Open-label Study to Evaluate Safety and Immunologic Response of COMBIG-DC Administered Intra-tumorally in Patients With Hepatocellular Carcinoma
The primary objective of this study is to answer the question "Is it possible to inject the COMBIG-DC vaccine in a hepatic tumor without getting unacceptable side effects"?
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
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.:
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.