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Hepatocellular CarcinomaPhase 2NCT04912765

Neoantigen Dendritic Cell Vaccine and Nivolumab in HCC and Liver Metastases From CRC

A Phase 2 study testing Neoantigen Dendritic Cell Vaccine and Nivolumab in people with Hepatocellular Carcinoma and Hepatocellular Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single arm phase II study of adjuvant intra-dermal NA DC vaccine combined with intravenous nivolumab in patients with resectable HCC (group A) or CRLM (group B) planned for curative surgery (with/without local ablation). Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Neoantigen Dendritic Cell Vaccine and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteSingapore
Study dates
15 Apr 2021to Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

Who may be able to join

  • HCC specific criteria (Group A):
  • Participants must have either newly diagnosed or recurrent HCC, confirmed by histology/cytology or clinically by AASLD criteria in cirrhotic subjects amenable for management with curative intent by resection (with or without the addition of local ablation), if they fulfil the following radiological criteria.
  • Up to three tumours, at least one with a diameter > 3cm
  • More than three tumours, none with a diameter > 5 cm
  • Recurrent HCCs are permitted if they were previously treated with curative intent (e.g. by surgery or ablative methods) and with liver-limited recurrence fulfilling criteria (a) and (b)
  • Child-Pugh Score 5 or 6
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  • All participants are required to have imaging studies (CT chest, tri-phasic CT/MRI of the liver, contrast-enhanced CT/MRI of abdomen and pelvis and other suspected/known sites of disease, and bone scans if indicated) confirming no-extra-hepatic metastatic disease within 12 weeks prior to study enrolment.
  • CRLM specific criteria (Group B):
  • Patients with histologically- or cytologically-diagnosed colorectal cancer with liver-limited metastases are eligible to enrol if:
  • There are no other sites of metastases aside from the liver confirmed by imaging studies (contrast-enhanced CT chest, abdomen and pelvis or contrast-enhanced CT chest and MRI abdomen and pelvis and other suspected sites of disease, and bone scans if indicated) at least 12 weeks prior to study enrolment AND
  • The liver metastases are amenable and planned for curative surgical resection with or without the addition of local ablation AND
  • The primary colorectal tumour had previously been resected or is amendable and planned for surgical resection.
  • Participants must have received peri-operative chemotherapy or are being planned for adjuvant chemotherapy after curative surgical resection
  • Participants with rectal cancer who received neoadjuvant radiation or are planned for adjuvant radiation are allowed into the study.
  • General Inclusion Criteria:
  • Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
  • Non-HBV non-HCV related HCC
  • HBV-HCC:
  • Resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen), OR
  • Chronic HBV infection as evidenced by detectable HBV surface antigen or HBV DNA. Participants with chronic HBV infection must be on antiviral therapy
  • HCV-HCC:
  • Resolved HCV infection as evidenced by detectable antibody, OR
  • Chronic HCV infection as evidenced by detectable HCV RNA.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Screening laboratory values must meet the following criteria, and should be obtained within 28 days prior to study enrolment:
  • Adequate hematologic function:
  • WBC ≥ 2,000/μL (stable, off any growth factor within 4 weeks of study treatment administration);
  • Neutrophils Absolute ≥ 1,500/μL (stable, off any growth factor within 4 weeks of study treatment administration);
  • Hemoglobin ≥ 8.5 g/dL (may be transfused to meet this requirement);
  • Platelet count ≥ 60 × 103/μL (transfusion to achieve this level is not permitted);
  • Adequate hepatic function:
  • Serum albumin > 2.8 g/L (transfusion to meet this level is not permitted); and
  • Serum total bilirubin < 3 mg/dL, and
  • Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 5 × ULN;
  • Prothrombin time (PT)-international normalized ratio (INR) < 2.3 or Prothrombin time (PT) < 6 seconds (transfusion to achieve this level is not permitted)
  • Adequate renal function with a serum creatinine of < 1.5 × ULN or a creatinine clearance > 40 mL/min (Cockcroft-Gault formula)
  • Age and Reproductive Status:
  • Males and females, ages 21 or older.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
  • Women must not be breastfeeding.
  • WOCBP must agree to follow instructions for method(s) of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.
  • Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.

Who cannot join

  • HCC specific criteria (Group A):
  • Target Disease Exceptions
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • Any evidence of tumour metastasis or co-existing malignant disease.
  • Participants showing evidence of macrovascular invasion on imaging tests.
  • Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation.
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  • Participants previously receiving any prior systemic therapy, trans-arterial embolization or chemoembolisation (TAE/TACE), selective internal radiation therapy (SIRT) and stereotactic radiation therapy (SBRT) for HCC.
  • CRLM specific criteria (Group B)
  • Target Disease Exceptions a) Patients with extra-hepatic colorectal metastases.
  • General Inclusion Criteria:
  • Medical Conditions
  • Active co-infection with:
  • Both hepatitis B and C as evidenced by detectable HBV surface antigen (HBs Ag) or HBV DNA and HCV RNA, OR
  • Hepatitis D infection in participants with hepatitis B
  • Known positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
  • 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 enroll.
  • Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Prior/Concomitant Therapy
  • Participants receiving or expected to receive IFN-based therapies during the study period.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to start of therapy.
  • Physical and Laboratory Test Findings
  • Positive pregnancy test
  • Allergies and Adverse Drug Reaction
  • History of severe hypersensitivity to a monoclonal antibody.
  • History of allergy or hypersensitivity to study drug components
  • Other Exclusion Criteria
  • Prisoners or participants who are involuntarily incarcerated.
  • Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Dr Shuting HAN contact

+65 6436 8000

han.shuting@singhealth.com.sg

Singapore1 site, 1 recruiting

  • National Cancer Center Singapore

    Singapore, 169690

    Recruiting

Other trials in Singapore

About this study

Official title: An Open Label, Single-arm, Phase II Neoantigen (NA) Dendritic Cell (DC) Vaccine and Anti-PD1 (Nivolumab) as Adjuvant Treatment in Resected Hepatocellular Carcinoma (HCC) (Group A) and Liver Metastases From Colorectal Cancer (CRLM) (Group B)

This is a single arm phase II study of adjuvant intra-dermal NA DC vaccine combined with intravenous nivolumab in patients with resectable HCC (group A) or CRLM (group B) planned for curative surgery (with/without local ablation).

Read the detailed description

Participants will be consented prior to resection of HCC and CRLM. Genomic sequencing of patient's blood and resected tumour will be performed, followed by tumour NA prediction and production. Patients will undergo venesection to generate DCs which will be pulsed with autologous NAs to produce the vaccine. 10 dose of intra-dermal NA DC vaccine will be administered every 2 weeks together with IV nivolumab (starting from the second vaccine dose). Patients will subsequently continue on adjuvant nivolumab to complete 1 year of treatment.

Efficacy will be evaluated based on relapse-free survival (RFS) at 24 months from surgery and the analyses of specific anti-NA immune responses of autologous peripheral T cells by ELISPOT and/or ICS assays. Safety data will also be obtained for patients who have received at least one dose of treatment.

Being tested
Neoantigen Dendritic Cell Vaccine, Nivolumab
Keywords
Tumour neoantigens, Tumor neoantigens, Cancer vaccine, Colorectal Cancer, Hepatocellular Cancer, Immunotherapy, anti-PD1
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms, Colorectal Neoplasms

What participants receive

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

  • Neoantigen Dendritic Cell VaccineBiological

    10 doses of the vaccine will be administered via intra-dermal injection concurrently with adjuvant nivolumab.

  • NivolumabDrug

    Also called Opdivo

    9 doses of 240mg IV nivolumab as a 30 minutes infusion will be administered in combination with NA DC vaccine starting from the second vaccine dose. Upon completion of 10 doses of NA DC vaccine, 480mg IV nivolumab will be administered as a 30 minutes infusion for a maximum of 9 doses.

Study groups in NCT04912765
Study groupRoleWhat they receive
Neoantigen Dendritic Cell Vaccine and NivolumabExperimentalNA DC vaccine every 2 weeks at a dose of 3-5 million cells. Adjuvant nivolumab every 2 weeks at 240mg when given concurrently with the vaccine; every 4 weeks at 480mg after vaccine treatment is completed for a total duration of 1 year.
Receives: Biological: Neoantigen Dendritic Cell Vaccine; Drug: Nivolumab

What is being measured

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

  1. 24-month Relapse Free Survival

    To investigate the clinical efficacy of combining NA DC vaccine with nivolumab in resected HCC and resected CRLM patients.

    Measured: Time from liver resection to first documented disease recurrence or death by any cause, up to 2 years

  2. Induced immune response against vaccinated NAs

    To determine the presence of NA specific T cells in resected HCC and resected CRLM patients after vaccination. Assessed by EPISOT and/or intracellular cytokine staining (ICS) assay with NA peptides in post-vaccination peripheral blood mononuclear cells (PBMC) compared to pre-vaccination PBMCs.

    Measured: Time from liver resection to first documented disease recurrence or death by any cause, up to 2 years

Secondary outcomes (2)

  1. Frequency and severity of treatment-emergent adverse events (AE)

    To determine the safety and tolerability of combining NA DC vaccine and nivolumab

    Measured: From the time of start of first treatment administered until 100 days after last dose of study treatment

  2. Overall Survival

    Measured: From time of start of study enrolment to death due to any cause, up to 7 years

Timeline

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

  1. First posted3 Jun 2021
  2. Study start15 Apr 2021
  3. Primary completionDec 2026 (estimated)
  4. Study completionJun 2027 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04912765
Sponsor's protocol ID
CA209-7R9
Status last verified
Jul 2026
First submitted
24 May 2021
Last updated
31 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoantigen Dendritic Cell Vaccine and Nivolumab in people with Hepatocellular Carcinoma and Hepatocellular Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.

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 43 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 31 Jul 2026. 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 Singapore. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Dr Shuting HAN (+65 6436 8000, han.shuting@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

24-month Relapse Free Survival (time frame: Time from liver resection to first documented disease recurrence or death by any cause, up to 2 years). The study lists 2 primary outcomes in all. 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 NCT04912765.

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 31 Jul 2026.

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