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AzTrials

HCCPhase 2NCT04588051

Cabozantinib in Hepatocellular Carcinoma

A Phase 2 study testing Cabozantinib in people with HCC, run by Stephen Chan Lam at 2 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

There have been lack of clinical studies on the role of drug treatment in patients who develop progressive disease with immune checkpoint inhibitors. Amongst HCC patients who become intolerant or refractory to sorafenib, cabozantinib has been shown by phase III clinical trial (CELESTIAL) to prolong the overall… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HCC
What is being tested?
Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesin 2 countries
Study dates
1 Nov 2020to 31 Dec 2028
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of HCC according to AASLD guidelines
  • Disease that is not amenable to a curative treatment (e.g. surgery, transplant, radiofrequency ablation)
  • Prior treatment with immune check-point inhibitor (including anti-PD1, anti-CTLA4, anti-PD1 plus anti-CTLA4, or above agents plus other targeted agents)
  • For patients who stop immune check-point inhibitor due to progressive disease, the duration of immune check-point inhibitor must be 8 weeks or longer
  • Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically nonsignificant and/or stable on supportive therapy
  • Life expectancy of 12 weeks or longer
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  • Age ≥ 18 years old
  • ECOG performance status of 0, 1 or 2
  • Adequate hematological function
  • Absolute neutrophil count (ANC) ≥ 1.2 x109/L
  • Platelets ≥ 60 x 109/L
  • Hemoglobin ≥ 8g/dL
  • Adequate renal function
  • serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation) AND
  • urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein < 1 g
  • Child-Pugh Score of A5 or 6
  • Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L)
  • Serum albumin > 2 g/dL (> 20 g/L)
  • Alanine aminotransferase (ALT) < 3.0 upper limit of normal (ULN)
  • Hemoglobin A1c (HbA1c) ≤ 8%
  • Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
  • Capable of understanding and complying with the protocol requirements and signed informed consent
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
  • Female subjects of childbearing potential must not be pregnant at screening.

Who cannot join

  • Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
  • Prior cabozantinib treatment
  • More than two lines of systemic therapy (i.e. cabozantinib must be either 2nd line or 3rd line systemic treatment)
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization.
  • Concurrent steroid use of prednisolone >10mg once daily
  • Presence of thrombosis or tumor invasion in inferior vena cava
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  • Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low dose LMWH are permitted.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months iv. Thromboembolic event within 3 months. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumour are eligible b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation/bleeding: i. Tumours invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months
  • Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before registration. Subjects with clinically relevant co d. Cavitating pulmonary lesion(s) or endobronchial disease
  • Lesion invading a major blood vessel (eg, pulmonary artery or aorta)
  • Clinically significant bleeding risk including the following within 3 months of registration: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors
  • Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
  • Moderate or severe ascites (Radiologically detected but clinically insignificant ascites is allowed)
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 21 days of registration Note: If the QTcF is > 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations
  • Pregnant or lactating females
  • Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy
  • Other clinically significant disorders that are judged by investigators to be unsuitable for the clinical trial

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Hong Kong1 site

  • Department of Clinical Oncology, Prince of Wales Hospital

    Hong Kong

Other trials in Hong Kong

South Korea1 site

  • ASAN Medical Center

    Seoul

Other trials in South Korea

About this study

Official title: A Phase II Clinical Trial to Study the Efficacy of Cabozantinib in Patients With Hepatocellular Carcinoma Refractory to Checkpoint Inhibitors

There have been lack of clinical studies on the role of drug treatment in patients who develop progressive disease with immune checkpoint inhibitors. Amongst HCC patients who become intolerant or refractory to sorafenib, cabozantinib has been shown by phase III clinical trial (CELESTIAL) to prolong the overall survival of patients, as compared to placebo. It is expected more patients will be treated with immune checkpoint inhibitors in future, hence it is clinically important to study the efficacy and toxicity of cabozantinib after treatment with immune checkpoint inhibitors.

Further, both MET activation and upregulation of regulatory T cells are implicated in resistance mechanism to immune checkpoint inhibitors. Immuno-modulatory effects of cabozantinib have been described in vitro and in murine models for several cancers. Moreover, cabozantinib appears to exert its effect on regulatory T cells (Tregs) via the HGF/c-Met pathway, where this receptor signaling cascade mediates multiple immune cell functions. HGF was shown to suppress DC function and in turn induce Tregs (CD4+ CD25+ FoxP3) in a murine central nervous system (CNS) autoimmunity model. HGF cultured monocytes differentiate into monocytic cells that produce soluble factors that favor immune suppressive conditions ideal for tumor progression. Above immunomodulatory effects could enable cabozantinib to reverse the immunosuppressive phenotype in patients after failure with immune checkpoint inhibitors.

The starting dose of cabozantinib of 60mg once daily in the current study is chosen in accordance with approved dose by FDA for treatment of advanced HCC

Conditions
HCC
Being tested
Cabozantinib

What participants receive

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

Study groups in NCT04588051
Study groupRoleWhat they receive
CabozantinibExperimentalNot described
Receives: Drug: Cabozantinib

What is being measured

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

  1. Median Progression-free survival (PFS)

    Measured: 1 year

Secondary outcomes (6)

  1. Median Overall survival (OS)

    Measured: 1 year

  2. Survival rate at 1-year

    Measured: 1 year

  3. Median time-to-progression

    Measured: 1 year

  4. Radiological response rate (RR) according to RECIST 1.1

    Measured: 1 year

  5. Radiological disease control rate (DCR) according to RECISIT 1.1

    Measured: 1 year

  6. Rate of adverse events according to CTCAE v5.0

    Measured: 1 year

Timeline

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

  1. First posted19 Oct 2020
  2. Study start1 Nov 2020
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04588051
Sponsor's protocol ID
HCC063
Status last verified
Mar 2026
First submitted
7 Oct 2020
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chan SL, Ryoo BY, Mo F, Chan LL, Cheon J, Li L, Wong KH, Yim N, Kim H, Yoo C. Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment. J Hepatol. 2024 Aug;81(2):258-264. doi: 10.1016/j.jhep.2024.03.033. Epub 2024 Apr 1.

    PubMed 38570034

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with HCC, run by Stephen Chan Lam 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 24 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 4 Mar 2026. 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 Hong Kong, South Korea. 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?

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?

Median Progression-free survival (PFS) (time frame: 1 year). 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 NCT04588051, 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 4 Mar 2026.

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