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Hepatocellular Carcinoma (HCC)Phase 2CAPIONCT07151326

Cabozantinib for Progressive HCC Post-first-line Immuno-oncologic Combination Therapy

A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma (HCC), run by National Health Research Institutes, Taiwan at 9 sites in Taiwan.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

1. To investigate the efficacy and safety of cabozantinib in patients with progressive HCC after ICI-based combination treatment. 2. To explore potential tissue and peripheral blood biomarkers associated with clinical benefits of cabozantinib, and resistance mechanisms of prior ICI and cabozantinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma (HCC)
What is being tested?
Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
9 sitesTaiwan
Study dates
Sep 2025to Jun 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

  • Understood and signed the informed consent form
  • Ability to comply with all protocol requirements
  • Age ≥ 18 years when signing informed consent form
  • Diagnosis of HCC confirmed by histology
  • Disease progression following prior first-line ICI-based combination therapy (only atezolizumab plus bevacizumab or tremelimumab plus durvalumab is permitted. Any liver-directed locoregional therapies administered during the treatment period of the first-line ICI-based combination therapy are allowed.
  • Disease that is not amenable to curative surgical and/or locoregional therapies (e.g. surgery, transplant, radiofrequency ablation)
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  • At least one measurable target lesion (per RECIST v1.1) that has not been previously treated with local therapy (e.g., radiofrequency ablation, cryoablation, transarterial embolization, transaraterial chemoembolization, radiotherapy, etc.) or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Child-Pugh A of liver reserve
  • Adequate hematologic and biochemical profiles:
  • White blood cells (WBC) ≥ 3,000/μL and absolute neutrophil count (ANC) ≥ 1,200/μL without granulocyte colony-stimulating factor support within 1 week before registration
  • Platelets (PLT) ≥ 60,000/μL without transfusion within 1 week before registration
  • Hemoglobin (Hb) ≥ 8 g/dL without transfusion within 1 week before registration
  • Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation)
  • Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) ≤5 × ULN
  • Serum total bilirubin (T-Bil) ≤ 2× ULN
  • Serum albumin (Alb) > 28 g/L (2.8 g/dL)
  • Urinalysis for proteinuria < 2+. Patients discovered to have ≥ 2+ proteinuria on urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.
  • Recovery to grade 1 from AEs related to any prior treatments, unless the AEs are clinically nonsignificant and/or stable on supportive therapy
  • Subjects with chronic hepatitis B virus (HBV) infection (defined as HBV surface antigen. positive; HBsAg+) must receive antiviral therapy with nucleoside analogs according to the local guidance throughout the study
  • 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 study and for 4 months after the last dose of study treatment
  • Life expectancy of 12 weeks or longer

Who cannot join

  • Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
  • Prior cabozantinib treatment
  • Any systemic anti-cancer therapy administered after discontinuation of the first-line immune checkpoint inhibitor-based combination
  • Prior liver-directed locoregional therapy administered within 4 weeks before registration
  • Any liver-directed locoregional therapy performed after progression with the first-line immune checkpoint inhibitor-based combination, but palliative radiotherapy for symptomatic bone metastasis is allowed
  • 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 registration
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  • Presence of tumor thrombosis or invasion in inferior vena cava (IVC), a major arterial blood vessel (e.g., pulmonary artery or aorta) or heart
  • Subjects with HBV DNA > 2000 IU/mL or detectable hepatitis C virus (HCV) RNA
  • Subjects refuse to provide tumor biopsy specimens within 4 weeks before registration
  • 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.
  • (Note: Low dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low dose LMWH (e.g. 40 mg Enoxaparin) for prophylaxis of venous thromboembolism are permitted)
  • Subjects with uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
  • Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mm Hg, or diastolic BP > 100 mm Hg despite optimal antihypertensive treatment
  • Stroke (including transient ischemic attack), myocardial infarction, or other ischemic event within 6 months
  • Thromboembolic event within 3 months. (Note: Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumour are eligible)
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation/bleeding:
  • Tumours invading the GI tract, 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
  • Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months
  • Major surgery within 2 months before registration. Complete healing from major surgery must have occurred 1 month before registration. Complete healing from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days before registration
  • Clinically significant bleeding risk including the following within 3 months before registration: upper GI bleeding (including gastroesophageal varices bleeding), hematuria, 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
  • Moderate or severe ascites (radiologically detected but clinically insignificant ascites without any diuretics or palliative paracentesis is allowed)
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 4weeks before 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)
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations
  • Inability in swallowing tablets
  • Pregnant or lactating females
  • Diagnosis of another malignancy within 2 years before registration, 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

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

Bor-Rong Chen contact

886-2-26534401 ext. 25162

brong@nhri.edu.tw

Ying-Chun Shen contact

9 sites in 1 country

Taiwan9 sites

  • Chang-Gung Memorial Hospital, Kaohsiung

    Kaohsiung City

    Yen-Yang Chen, MD

    Yen-Yang Chen, MD

  • Taichung Veterans General Hospital

    Taichung, 407

    Teng-Yu Lee, MD, PhD

    Teng-Yu Lee, MD, PhD

  • China Medical University Hospital

    Taichung

  • National Cheng-Kung University Hospital

    Tainan

    Yih-Jyh Lin, MD

    Yih-Jyh Lin, MD

  • National Taiwan University Hospital

    Taipei, 100

    Ying-Chun Ying-Chun, MD, PhD

    Ying-Chun Ying-Chun, MD, PhD

  • Mackay Memorial Hospital

    Taipei, 104

    Ching-Wei Chang, MD, MS

    Ching-Wei Chang, MD, MS

  • Taipei Veterans General Hospital

    Taipei

    Yi-Hsiang Huang, MD, PhD

    Yi-Hsiang Huang, MD, PhD

  • Tri-Service General Hospital

    Taipei

    Ming-Shen Dai, MD, PhD

    Ming-Shen Dai, MD, PhD

  • Chang Gung Memorial Hospital (Lin-Kou),

    Taoyuan

    Po-Ting Lin, MD

    Po-Ting Lin, MD

Other trials in Taiwan

About this study

Official title: A Phase II, Single-arm, Multi-center Trial of Cabozantinib for Progressive Hepatocellular Carcinoma (HCC) Post-first-line Immuno-oncologic Combination Therapy (CAPIO Study)

  1. To investigate the efficacy and safety of cabozantinib in patients with progressive HCC after ICI-based combination treatment.
  2. To explore potential tissue and peripheral blood biomarkers associated with clinical benefits of cabozantinib, and resistance mechanisms of prior ICI and cabozantinib.
Read the detailed description

Immune checkpoint inhibitor (ICI)-based combination therapy, such as atezolizumab-bevacizumab or tremelimumab-durvalumab, has become the current standard first-line treatment for advanced hepatocellular carcinoma (HCC). However, there is no approved second-line treatment yet following progression on these ICI-based combination therapies. Multikinase inhibitors (MKIs), such as lenvatinib, sorafenib, cabozantinib, and regorafenib, are often recommended by established guidelines, expert consensus, and retrospective studies. However, this approach lacks robust evidence from prospective studies or reliable biomarkers for patient selection.

Cabozantinib, a MKI targeting vascular endothelial growth factor receptor (VEGFR), MET, and the TAM family of kinases (TYRO3, AXL, and MER), is one of the standard post-sorafenib treatments for advanced HCC. It has shown comparable effectiveness to sorafenib in the first-line setting. The safety profile of cabozantinib is well established and manageable.

Furthermore, cabozantinib offers several advantages that make it a rational treatment option after ICI failure:

  1. Potent VEGFR inhibition: Cabozantinib effectively inhibits angiogenesis, which is essential for tumor growth.
  2. Additional AXL inhibition: Cabozantinib targets AXL, which is a key mediator of tumor progression and ICI resistance across different cancer types.
  3. Clinical evidence: A recent phase II trial demonstrated that around 30% of patients receiving cabozantinib after progression with ICIs remained progression-free at 6 months, despite an objective response rate of 6%. This underscores the need for biomarkers to identify patients who are more likely to benefit from cabozantinib after ICI failure.

In this trial, the investigators aim to investigate the efficacy and safety of cabozantinib in HCC patients who have progressed on first-line ICI-based combination. Additionally, the investigators will explore tumor tissue and peripheral blood biomarkers for clinical benefits of cabozantinib, and resistance mechanisms of prior ICI and current cabozantinib.

Being tested
Cabozantinib
Keywords
Tyrosine kinase inhibitor, Immune checkpoint inhibitor, Multikinase inhibitors
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • CabozantinibDrug

    Also called Cabometyx®

    All patients will be treated with cabozantinib at 60 mg once daily.

Study groups in NCT07151326
Study groupRoleWhat they receive
CabozantinibExperimentalAll patients will be treated with cabozantinib at 60 mg once daily.
Receives: Drug: Cabozantinib

What is being measured

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

  1. Progression-free rate at 6 months

    The percentage of subjects remaining progression (per RECIST v1.1) -free at 6 months after initiation of study treament .

    Measured: 30 months

  2. Treatment-emergent adverse event

    Incidence of treatment-emergent adverse events

    Measured: 30 months

Timeline

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

  1. First posted3 Sep 2025
  2. Study startSep 2025 (estimated)
  3. Primary completionJun 2028 (estimated)
  4. Study completionJun 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
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07151326
Sponsor's protocol ID
T 1225
Other IDs
T1225
Acronym
CAPIO
Status last verified
Aug 2025
First submitted
14 Aug 2025
Last updated
3 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Invetigator Initial Trial

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma (HCC), run by National Health Research Institutes, Taiwan at 9 sites in Taiwan.

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 22 inclusion and 28 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: opening soon, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Taiwan. 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 Bor-Rong Chen (886-2-26534401 ext. 25162, brong@nhri.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free rate at 6 months (time frame: 30 months). 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 NCT07151326.

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 3 Sep 2025.

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