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Hepatocellular CarcinomaPhase 2/3TACE-3NCT04268888

Nivolumab in Combination With TACE/TAE for Patients With Intermediate Stage HCC

A Phase 2/3 study testing Nivolumab and TACE/TAE and TACE/TAE in people with Hepatocellular Carcinoma, run by The Clatterbridge Cancer Centre NHS Foundation Trust at 2 sites in 2 countries.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This study evaluates the addition of nivolumab to TACE/TAE in the treatment of patients with intermediate stage hepatocellular carcinoma. All patients will receive TACE/TAE and half will receive nivolumab. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Nivolumab and TACE/TAE and TACE/TAE
Could I receive a placebo?
No, everyone receives an active treatment
How many people
522 participants
Where
2 sitesin 2 countries
Study dates
8 May 2019to 30 Jun 2026
Phase
Phase 2/3
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histological diagnosis of HCC and at least one uni-dimensional lesion measurable according to RECIST 1.1 criteria by CT-scan or MRI.
  • Not a candidate for surgical resection or liver transplantation
  • Aged ≥16 years and estimated life expectancy >3 months
  • ECOG performance status 0-1
  • Adequate haematological function:
  • Hb ≥9g/L
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  • Absolute neutrophil count ≥1.0x109/L
  • Platelet count ≥60x109/L
  • Bilirubin ≤50 μmol/L, AST,ALT and ALP ≤5 x ULN
  • Adequate renal function; Creatinine ≤ 1.5ULN (Using Cockcroft-Gault Formula)
  • INR ≤1.6
  • Child-Pugh A (score ≤6) (Appendix D)
  • HAP score A, B or C (Appendix E)
  • No contra-indications to T-cell checkpoint inhibitor therapy (use of immunosuppressive drugs including steroids at dose equivalent to prednisolone >10mg/day unless used as replacement therapy; organ transplantation; subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, lichen planus or other conditions not expected to recur in the absence of an external trigger are permitted to enrol).
  • Women of child-bearing potential should have a negative pregnancy test prior to study entry. Both men and women must be using an adequate contraception method, which must be continued for 5 months after completion of treatment for women and 7 months for men
  • Written informed consent

Who cannot join

  • Extrahepatic metastasis
  • Prior embolisation, systemic or radiation therapy for HCC
  • Any contraindications for hepatic embolisation procedures including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis
  • Investigational therapy or major surgery within 4 weeks of trial entry
  • History of variceal bleeding within the past 4 weeks
  • Child-Pugh cirrhosis B or C (score ≥7)
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  • HAP score D
  • Hepatic encephalopathy
  • Ascites refractory to diuretic therapy
  • Documented occlusion of the hepatic artery or main portal vein5
  • Hypersensitivity to intravenous contrast agents
  • Active clinically serious infection > Grade 2 NCI-CTC
  • Pregnant or lactating women
  • Known history of HIV infection
  • HBV chronic infection with HBV DNA > 500IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated.
  • 17. History of second malignancy except those treated with curative intent more than three years previously without relapse and non-melanotic skin cancer or cervical carcinoma in situ 18. Evidence of severe or uncontrolled systemic disease, or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial 19. Psychiatric or other disorder likely to impact on informed consent 20. Patient is unable and/or unwilling to comply with treatment and study instructions 20. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity
  • 21. Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or antifungal therapy within 7 days prior to administration of study medication
  • 22. Positive test for latent TB or evidence of active TB
  • 23. Hypersensitivity to any of the active substances or excipients
  • 24. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment
  • 25. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration
  • 26. Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis
  • 27. 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 enrol

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

France1 site

  • Unicancer

    Paris, cedex 13

Other trials in France

United Kingdom1 site

  • University of Liverpool

    Liverpool, L69 7ZB

Other trials in United Kingdom

About this study

Official title: A Two-arm Multi-stage (TAMS) Seamless Phase II/III Randomised Trial of Nivolumab in Combination With TACE/TAE for Patients With Intermediate Stage HCC

This study evaluates the addition of nivolumab to TACE/TAE in the treatment of patients with intermediate stage hepatocellular carcinoma. All patients will receive TACE/TAE and half will receive nivolumab.

Read the detailed description

A significant proportion of HCC patients present with, or progress to, intermediate stage disease and these patients are typically treated with transarterial chemo-embolisation (TACE) or transarterial embolisation (TAE).

However, since TACE/TAE is generally a palliative therapy, it provides a potential backbone for the addition of effective systemic therapies with the aim of improving survival outcomes. Since TACE may liberate an abundance of tumour antigens and 'danger' signals, it may lend itself to combination with immunotherapeutic strategies.

Nivolumab is a human monoclonal antibody. Nivolumab targets the programmed death-1 PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.

Being tested
Nivolumab and TACE/TAE, TACE/TAE
Keywords
Intermediate Stage
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • Nivolumab and TACE/TAEDrug

    Immunotherapy and TACE/TAE

  • TACE/TAEProcedure or surgery

    TACE/TAE (as per local practice)

Study groups in NCT04268888
Study groupRoleWhat they receive
TACE/TAE AloneActive comparatorTransarterial Chemoembolisation (TACE) and/or Transarterial Embolisation (TAE) Alone.
Receives: Procedure: TACE/TAE
TACE/TAE and NivolumabExperimentalAs above for TACE/TAE. Nivolumab adminstered as a flat dose of 480mg IV.
Receives: Drug: Nivolumab and TACE/TAE; Procedure: TACE/TAE

What is being measured

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

  1. Overall Survival - phase III primary outcome

    Measured in days

    Measured: The time until death. Patients discontinuing the study, lost to follow-up or still alive at the end of the study will be censored at the last know date alive, this can be assessed up until 2 years after the last patient.

  2. Time to TACE Progression (TTTP) - phase II primary outcome

    Measured in days

    Measured: The time to confirmatory scan 4 weeks after progression this can be assessed up until 2 years after the last patient is randomised

Secondary outcomes (5)

  1. Time to Progression

    Measured in days

    Measured: Time to date of progression confirmed by RECIST1.1 assessed up until 2 years after the last patient is randomised

  2. Radiological response rate

    RECIST 1.1

    Measured: Through study completion

  3. Safety and Toxicity: the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE)

    the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE), measured and categorised based on CTCAE (version 4).

    Measured: Through study completion

  4. Progression Free Survival

    Measured in days

    Measured: Time to progression or death. Assessed up until 2 years.

  5. QOL: EORTC QLQ-C30

    QoL will be scored according to the EORTC QLQ-C30 manual and guidelines.

    Measured: baseline, pre - TACE (first treatment) and 12 weekly thereafter until end of treatment. Assessed up until 2 years after the last patient is randomised

Timeline

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

  1. First posted13 Feb 2020
  2. Study start8 May 2019
  3. Primary completion1 Aug 2025 (estimated)
  4. Study completion30 Jun 2026 (estimated)

Why it stopped: Analysis meant the study should close to recruitment

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients shall be randomised on a 1:1 basis throughout the study and allocated using pre-generated lists produced by the study statistician. List shall be produced using permuted blocks algorithm with random block sizes of 2 and 4. Stratification factors used in the study are randomising centre, baseline HAP score (A vs. B vs. C) and vascular invasion (No vs. Yes).
Masking
None (open label)
Enrolment
522 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04268888
Sponsor's protocol ID
CA209-9Y9
Acronym
TACE-3
Status last verified
Feb 2025
First submitted
5 Jun 2019
Last updated
26 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1:137-149. doi: 10.1002/hep.31424. Epub 2020 Nov 6. No abstract available.

    PubMed 32557715

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Nivolumab and TACE/TAE and TACE/TAE in people with Hepatocellular Carcinoma, run by The Clatterbridge Cancer Centre NHS Foundation Trust at 2 sites in 2 countries.

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 16 inclusion and 23 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: paused, as of the sponsor's last update on 26 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France, United Kingdom. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Results are not available in the source record.

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?

Overall Survival - phase III primary outcome (time frame: The time until death. Patients discontinuing the study, lost to follow-up or still alive at the end of the study will be censored at the last know date alive, this can be assessed up until 2 years after the last patient.). 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 NCT04268888, 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 26 Feb 2025.

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