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

NCT04472767 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20205807UCI 19-49
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma; HCC

Keywords

Hepatocellular Carcinoma; HCC; Cabozantinib; Ipilimumab; Nivolumab; TACE; transarterial chemoembolization

Outcome Measures

Primary Outcomes (2)

• 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.

  6 months

• 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.

  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)

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

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

• Percentage of Grade 3-5 Adverse Events

  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.

• Progression Free Survival

  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.

• Conversion Rate to Resectable

  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.

Study Arms (1)

Cabozantinib with Ipilimumab/Nivolumab and TACE

EXPERIMENTAL

Subjects 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

Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib; Procedure: Transarterial Chemoembolization

Interventions

Nivolumab DRUG

Given IV

Also known as: OPDIVO®

Cabozantinib with Ipilimumab/Nivolumab and TACE

Ipilimumab DRUG

Given IV

Also known as: YERVOY®

Cabozantinib with Ipilimumab/Nivolumab and TACE

Cabozantinib DRUG

Given PO

Also known as: CABOMETYX®, COMETRIQ

Cabozantinib with Ipilimumab/Nivolumab and TACE

Transarterial Chemoembolization PROCEDURE

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.

Also known as: TACE

Cabozantinib with Ipilimumab/Nivolumab and TACE

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Exelixis: collaborator
• University of California, Irvine: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab; 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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Farshid Dayyani, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

CONTACT

1-877-827-7883; ucstudy@uci.edu

University of California Irvine Medical

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: July 11, 2020
• First Posted: July 15, 2020
• Study Start: August 7, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)