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Hepatocellular CarcinomaPhase 2NCT04472767

Cabozantinib Combined With Ipilimumab/Nivolumab and TACE in Patients With Hepatocellular Carcinoma

A Phase 2 study testing Nivolumab, Ipilimumab and Cabozantinib in people with Hepatocellular Carcinoma and HCC, run by University of California, Irvine at 1 site in United States.

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 phase 2 single-arm, open-label clinical trial determining efficacy of cabozantinib in combination with ipilimumab/nivolumab and transarterial chemoembolization (TACE) in subjects with hepatocellular carcinoma (HCC). These are subjects who are not candidates for curative intent treatment. 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?
Nivolumab, Ipilimumab and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
7 Aug 2020to 1 Sep 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologic or radiographic diagnosis of hepatocellular carcinoma
  • At least one lesion amenable to TACE treatment
  • Child-Pugh A-B7 (B7 based on Albumin allowed)
  • Not a candidate for resection or transplantation
  • Age ≥ 18 years.
  • Performance status: ECOG performance status ≤2
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  • Must have at least one measurable lesion (either untreated or progressed after previous locoregional treatment)
  • Adequate organ and marrow function as defined below:
  • Leukocytes ≥ 2,000/mcL
  • absolute neutrophil count ≥ 1000/mcL
  • platelets ≥ 60,000/mcl
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present
  • creatinine <1.5ULN
  • hemoglobin ≥ 8 g/dL
  • Serum albumin ≥ 2.8 g/dL
  • Urine protein/creatinine ration (UPCR) ≤ 1 mg/mg
  • The effects of cabozantinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Based on its mechanism of action, ipilimumab can cause fetal harm when administered to a pregnant woman. Females of reproductive potential must use effective contraception during treatment with ipilimumab and for 3 months following the last dose of ipilimumab.
  • Based on its mechanism of action, nivolumab can cause fetal harm when administered to a pregnant woman. Females of reproductive potential must use effective contraception during treatment with nivolumab and for 5 months following the last dose of nivolumab.
  • 1. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Life expectancy of greater than 3 months
  • Ability to swallow tablets
  • Ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • Any type of previous systemic anti-cancer treatment
  • All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
  • Any locoregional treatment for HCC within 3 months
  • Vp4 or Vp3 portal vein thrombus
  • Extrahepatic disease
  • Patients may not be receiving any other investigational agents.
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, cabozantinib or other agents used in study.
  • Concomitant anticoagulation with coumarin agents (eg, warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban), or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
  • Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose low molecular weight heparins (LMWH).
  • Therapeutic doses of LMWH in subjects with a screening platelet count > 100,000/μL, without known brain metastases, and who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 28 days before the first dose of study treatment.
  • Uncontrolled intercurrent illness including, but not limited to, the following conditions:
  • ongoing or active infection
  • symptomatic congestive heart failure
  • uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose
  • unstable angina pectoris
  • cardiac arrhythmia
  • evidence of tumor invading GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
  • Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.
  • Other clinically significant disorders that would preclude safe study participation:
  • Serious non-healing wound/ulcer/bone fracture
  • Uncompensated/symptomatic hypothyroidism
  • Moderate to severe hepatic impairment (Child-Pugh B or C)
  • psychiatric illness/social situations that would limit compliance with study requirements.
  • Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Prior treatment with cabozantinib
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
  • Corrected QT (QTc) = QT / ∛RR
  • QT: duration of QT interval RR: duration of RR interval
  • Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ and not treated with systemic therapy.
  • Inability to comply with study and follow-up procedures as judged by the Investigator
  • Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
  • Has fibrolamellar HCC
  • Has received prior cytotoxic, biologic or other systemic anticancer therapy including investigational agents within 4 weeks prior to randomization.
  • Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
  • Has severe hypersensitivity (Grade ≥ 3) to nivolumab or cabozantinib and/or any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Trial locations and contacts

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

Chao Family Comprehensive Cancer Center University of California, Irvine contact

1-877-827-7883

ucstudy@uci.edu

University of California Irvine Medical contact

United States1 site, 1 recruiting

  • Chao Family Comprehensive Cancer Center, University of California, Irvine

    Orange, California, 92868

    Farshid Dayanni, MD, PhD, 877-827-8839, ucstudy@uci.edu

    Recruiting

Other trials in United States

About this study

Official title: Phase 2 Study of Cabozantinib Combined With Ipilimumab/Nivolumab and Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC) Who Are Not Candidates for Curative Intent Treatment

This is a phase 2 single-arm, open-label clinical trial determining efficacy of cabozantinib in combination with ipilimumab/nivolumab and transarterial chemoembolization (TACE) in subjects with hepatocellular carcinoma (HCC). These are subjects who are not candidates for curative intent treatment.

Being tested
Nivolumab, Ipilimumab, Cabozantinib, Transarterial Chemoembolization
Keywords
Hepatocellular Carcinoma, HCC, Cabozantinib, Ipilimumab, Nivolumab, TACE, transarterial chemoembolization
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • NivolumabDrug

    Also called OPDIVO®

    Given IV

  • IpilimumabDrug

    Also called YERVOY®

    Given IV

  • CabozantinibDrug

    Also called CABOMETYX®, COMETRIQ

    Given PO

  • Transarterial ChemoembolizationProcedure or surgery

    Also called TACE

    TACE treatment will be administered using either the DEB-TACE or cTACE modality in a series of up to 3 individual procedures within the 9-12 weeks following Day 21 (= cycle 1 day 21) of a patient's first infusion of nivolumab/ipilimumab. The first TACE treatment should start no more than 7 working days after being cycle 1 day 21.

Study groups in NCT04472767
Study groupRoleWhat they receive
Cabozantinib with Ipilimumab/Nivolumab and TACEExperimentalSubjects receive Cabozantinib 40 mg daily on days 1-28 of a 28 day cycle, this is to be started 7-14 days after the last TACE procedure. Nivolumab 480 mg IV on day 1 of a 28 day cycle (cycle 2 and beyond), this is to be started 7-14 days after the last TACE procedure. Nivolumab: 3mg/kg IV on day 1 of a 21 day cycle x 1 dose. Ipilimumab: 1 mg/kg on day 1 of a 21 day cycle x 1 dose TACE: Within 3-4 weeks of cycle 1 day 1; may be done up to 3 times (9-12 weeks total), the intervals between each TACE treatment can vary based on investigator's discretion
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib; Procedure: Transarterial Chemoembolization

What is being measured

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

  1. Percentage of Participants with Progression-free Survival at 6 Months

    This is defined as the percentage of subjects who are free of progression 6 months after study treatment start. Progression is defined death, radiographic progression or clinical deterioration attributed disease progression as judged by an investigator. Radiographic progression is defined using the modified Response Evaluation Criteria in Solid Tumors Criteria (mRECIST), as a 20% increase in the sum of diameters of of viable (enhancing) target lesions and/or appearance of one or new lesions and/or unequivocal progression of existing non-target lesions.

    Measured: 6 months

  2. Complete Response Rate

    Complete Response (CR) is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

    Measured: From date of registration until first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

Secondary outcomes (4)

  1. Overall Survival of Patients who Received Cabozantinib with Ipilimumab/Nivolumab and TACE

    To evaluate overall survival in patients with advanced gastric and gastroesophageal adenocarcinoma treated with this combination of cabozantinib and irinotecan.

    Measured: From date of registration for up to 18 months after last patient is enrolled or until death from any cause, whichever came first.

  2. Percentage of Grade 3-5 Adverse Events

    To evaluate the tolerability of administering cabozantinib in combination with cabozantinib/nivolumab and TACE in patients with hepatocellular carcinoma from the start of treatment, duration of treatment and up to 4 weeks after completion of study treatment. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.

    Measured: From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

  3. Progression Free Survival

    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

  4. Conversion Rate to Resectable

    Rate of subjects suitable for liver transplant according to the Milan criteria. Milan criteria is defined as single tumors ≤5 cm in diameter or no more than three tumors ≤3 cm in diameter single tumors ≤5 cm in diameter or no more than three tumors ≤3 cm in diameter

    Measured: From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 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 posted15 Jul 2020
  2. Study start7 Aug 2020
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion1 Sep 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
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04472767
Sponsor's protocol ID
20205807
Other IDs
UCI 19-49
Status last verified
Apr 2026
First submitted
11 Jul 2020
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Cabozantinib in people with Hepatocellular Carcinoma and HCC, run by University of California, Irvine at 1 site in United States.

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 26 inclusion and 51 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 26 Oct 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 United States. 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 Chao Family Comprehensive Cancer Center University of California, Irvine (1-877-827-7883, ucstudy@uci.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Progression-free Survival at 6 Months (time frame: 6 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 NCT04472767.

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 Oct 2026.

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Clinical Trial NCT04472767 | AzTrials