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Hepatocellular CarcinomaPhase 1NCT01974661

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

A Phase 1 study testing COMBIG-DC (ilixadencel) in people with Hepatocellular Carcinoma, run by Mendus at 1 site in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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"? Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
COMBIG-DC (ilixadencel)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteSweden
Study dates
Oct 2013to 28 Jun 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 25Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

  • Dept. of Transplantation and Liver Surgery, Sahlgrenska University Hospital

    Gothenburg, SE-413 45

Other trials in Sweden

About this study

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

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"?

Read the detailed 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).

Being tested
COMBIG-DC (ilixadencel)
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • COMBIG-DC (ilixadencel)Biological

    Also called ilixadencel

    Allogenic dendrite-cell based therapeutic vaccine

Study groups in NCT01974661
Study groupRoleWhat they receive
COMBIG-DCExperimentalCOMBIG-DC (allogeneic dendritic cells) Cancer Vaccine 3 vaccinations: 5, 10 or 20 million cells per injection
Receives: Biological: COMBIG-DC (ilixadencel)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 6 months after last patient's last vaccination

Secondary outcomes (10)

  1. 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.

    Measured: Until 3 months after last vaccination

  2. 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

    Measured: Until 6 months after last patient's last vaccination

  3. Long term changes in ECOG scores

    Measured: 3 and 6 months after last vaccination

  4. Change in body weight

    Measured: 3 and 6 months after last vaccination

  5. 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.

    Measured: Up to 3 months after last vaccination

  6. Long term changes in Quality of Life scores

    Measured: 3 and 6 months after last vaccination

  7. 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.

    Measured: Up to 3 months after last vaccination

  8. Changes in HBV, HCV virus titers

    Changes in HBV, HCV virus titers vs baseline, for patients that are tested positive at screening

    Measured: Day 8 after each injection and at the 3 and 6 months visit

  9. To study time to progress (TTP)

    TTP measured as time from first dose of COMBIG-DC until radiologically proven progress according to mRECIST.

    Measured: Measured every 3 months until progression

  10. 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)

    Measured: Up to 6 months after last patient's last vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2013 (estimated)
  2. Study startOct 2013
  3. Primary completion28 Jun 2017
  4. Study completion28 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01974661
Sponsor's protocol ID
IM-102
Other IDs
2013-001787-31
Status last verified
Sep 2017
First submitted
21 Oct 2013
Last updated
29 Sep 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Rizell M, Sternby Eilard M, Andersson M, Andersson B, Karlsson-Parra A, Suenaert P. Phase 1 Trial With the Cell-Based Immune Primer Ilixadencel, Alone, and Combined With Sorafenib, in Advanced Hepatocellular Carcinoma. Front Oncol. 2019 Jan 21;9:19. doi: 10.3389/fonc.2019.00019. eCollection 2019.

    PubMed 30719425

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing COMBIG-DC (ilixadencel) in people with Hepatocellular Carcinoma, run by Mendus at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Registration of adverse events as a measure of safety and tolerability (time frame: Up to 6 months after last patient's last vaccination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01974661, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.

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