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

NCT07151326 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: T 1225T1225
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Tyrosine kinase inhibitor; Immune checkpoint inhibitor; Multikinase inhibitors

Outcome Measures

Primary Outcomes (2)

• 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 .

  30 months

• Treatment-emergent adverse event

  Incidence of treatment-emergent adverse events

  30 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

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

Also known as: Cabometyx®

Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Taiwan University Hospital: collaborator
• Taipei Veterans General Hospital, Taiwan: collaborator
• Tri-Service General Hospital: collaborator
• Mackay Memorial Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator
• China Medical University Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• National Cheng-Kung University Hospital: collaborator

Study Sites (9)

Chang-Gung Memorial Hospital, Kaohsiung

Kaohsiung City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Mackay Memorial Hospital

Taipei, 104, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital (Lin-Kou),

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Tsang-Wu Liu

  Taiwan Cooperative Oncology Group, NHRI

  STUDY CHAIR

• Ying-Chun Shen

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bor-Rong Chen

CONTACT

886-2-26534401; brong@nhri.edu.tw

Ying-Chun Shen

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: September 3, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (9)