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

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase I Open-label Study to Evaluate Safety and Immunologic Response of COMBIG-DC Administered Intra-tumorally in Patients With Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01974661
• Other study ID #: IM-102
• Secondary ID: 2013-001787-31
• Status: Completed
• Phase: Phase 1
• First received: October 21, 2013
• Last updated: September 27, 2017
• Start date: October 2013
• Est. completion date: June 28, 2017

Study information

• Verified date: September 2017
• Source: Immunicum AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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"?

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 28, 2017
• Est. primary completion date: June 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

2. 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.:

1. P-Prothrombincomplex (PK) >1.4,

2. Platelet count <50 75 x109/L

3. Leukocyte count <3.0 x 109/L

4. 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• COMBIG-DC (ilixadencel)
Allogenic dendrite-cell based therapeutic vaccine

Locations

Country	Name	City	State
Sweden	Dept. of Transplantation and Liver Surgery, Sahlgrenska University Hospital	Gothenburg

Sponsors (2)

Lead Sponsor	Collaborator
Immunicum AB	Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Local tissue changes in injected/non-injected tumor and surrounding tissue, assessed by MRI	An optional addition to the assessment of local procedural injuries (primary outcome).	1 month after each vaccination
Primary	Registration of adverse events as a measure of safety and tolerability	Changes in vital signs from baseline (heart rate, blood pressure, body temperature); Changes in lab parameters from baseline; Short term worsening in ECOG and/or Child Pugh and/or MELD score; Local procedural injuries, assessed by MRI or ultrasound	Up to 6 months after last patient's last vaccination
Secondary	To evaluate systemic inflammatory response	Potential systemic release of relevant cytokines, chemokines and other inflammatory parameters in blood;IL-1R, IL-2,IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF. GM-CSF, IFN-gamma, MCP-1, MIP-1 beta and TNF-alpha.	Until 3 months after last vaccination
Secondary	To evaluate tumor control	CT/MRI evaluation 3 and 6 months after first vaccination. Patients with stable disease or tumor response will continue tumor evaluation every 3rd month until progress or until last study patient has had his/her 6 month visit.; Measuring number of tumor specific T cells with flow cytometry after in vitro stimulation with different pools of HCC-associated tumor peptides (Alpha-feto protein (AFP), and hTERT); Measuring AFP (alpha-feto protein) levels in blood; Measuring the level of circulating tumor cell, identified as tested positive for MICA, EpCAM, CD133, CD34, CK18	Until 6 months after last patient's last vaccination
Secondary	Long term changes in ECOG scores		3 and 6 months after last vaccination
Secondary	Change in body weight		3 and 6 months after last vaccination
Secondary	To evaluate systemic immunological response	Vaccine cell tracking; PBMCs will be stained with antibodies specific for one HLA class I or one HLA-class II antigen that is selectively expressed on donor vaccine cells.; vaccine-induced alloimmunization; screening of alloantibodies against HLA-A, B, C (MHC-class I) and HLA-DR, DQ, DP (MHC-class II) antigens; autoimmune events; screening of autoantibodies against autoantigens, including nuclear antigens (ANA, SSA, SSB, Sm, RNP, Scl-70, Centromeres and Jo-1) and liver parenchyma-associated autoantigens (liver-kidney microsomal antigens and mitochondrial antigens); complement activation; classical/alternative complement function, C3, C4, C3d, and Factor-B.; immune cell occurrence and activation state; CD3+ , CD3+4+ and CD3+8+ T cells, CD19+ B-cells CD3-16+56+ NK-cells, CD3-16+56+69+ NK cells, CD3+16+56+ NKT-cells, CD3+16+56+69+ NKT-cells and CD3+HLA-DR+ T cells.	Up to 3 months after last vaccination
Secondary	Long term changes in Quality of Life scores		3 and 6 months after last vaccination
Secondary	To evaluate immunological response	complement activation; classical/alternative complement function, C3, C4, C3d, and Factor-B.; immune cell occurrence and activation state; CD3+ , CD3+4+ and CD3+8+ T cells, CD19+ B-cells CD3-16+56+ NK-cells, CD3-16+56+69+ NK cells, CD3+16+56+ NKT-cells, CD3+16+56+69+ NKT-cells and CD3+HLA-DR+ T cells.	Up to 3 months after last vaccination
Secondary	Changes in HBV, HCV virus titers	Changes in HBV, HCV virus titers vs baseline, for patients that are tested positive at screening	Day 8 after each injection and at the 3 and 6 months visit
Secondary	To study time to progress (TTP)	TTP measured as time from first dose of COMBIG-DC until radiologically proven progress according to mRECIST.	Measured every 3 months until progression
Secondary	To study overall survival (OS)	OS measured as survival time from first dose of COMBIG-DC until end of study or death (whichever comes first)	Up to 6 months after last patient's last vaccination