Actively Recruiting
A Phase II Randomized Study of Atezolizumab Plus Multi-Kinase Inhibitor Versus Multi-Kinase Inhibitor Alone in Patients With Advanced Unresectable Hepatocellular Carcinoma Previously Treated With Atezolizumab Plus Bevacizumab
Led by Academic and Community Cancer Research United · Updated on 2025-09-16
122
Participants Needed
16
Research Sites
52 weeks
Total Duration
On this page
Sponsors
A
Academic and Community Cancer Research United
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating whether combining atezolizumab with a multi-kinase inhibitor (cabozantinib or lenvatinib) is more effective than using a multi-kinase inhibitor alone in treating adults with advanced liver cancer that cannot be removed by surgery, has spread locally or to other parts of the body, and who have previously received treatment. This phase II trial aims to understand progression-free survival, overall survival, response rates, duration of response, and safety of these treatments in patients with this condition. Participants are randomly assigned to one of two groups. One group receives atezolizumab intravenously every 21 days along with either cabozantinib or lenvatinib taken orally daily for 21 days per cycle. The other group receives only cabozantinib or lenvatinib orally on the same schedule. Treatment continues unless the disease worsens or side effects become unacceptable. After treatment ends, patients are followed every 9 weeks for up to two years. During the study, patients will undergo evaluations including imaging and laboratory tests to monitor tumor response and side effects. Researchers will track overall survival and progression-free survival for up to three and two years respectively. Safety is monitored up to 30 days after the last dose. Participants must return for follow-up visits during the active monitoring phase. The trial helps understand how these therapies work together and their effects on advanced liver cancer.
CONDITIONS
Brief Title
Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide written informed consent within 28 days before randomization
- Willing to return to the enrolling institution for follow-up during active monitoring
- Age 18 years or older
- Hepatocellular carcinoma confirmed by diagnosis or clinical criteria
- Locally advanced, metastatic, or unresectable disease not suitable for curative treatment
- Previously progressed on atezolizumab plus bevacizumab as first-line therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Child Pugh class A liver function
- Documented hepatitis B and C virus status with specific treatment requirements for active HBV
- At least one measurable untreated malignant lesion per RECIST v1.1
- Consent to use archival tumor tissue if available
- Willingness to provide mandatory blood specimens for research
- Willingness to provide mandatory tissue specimens for the first 10 patients per arm at specified sites
- Adequate blood counts and liver function tests within 28 days prior to randomization
- Negative pregnancy test for women of childbearing potential within 14 days prior to randomization
- Resolution of prior treatment toxicities to grade 1 or less except alopecia and peripheral neuropathy
- Agreement to use two forms of medically approved contraception during and for 5 months after study treatment
- Ability to take oral medications
You will not qualify if you...
- Diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma, or mixed hepatocellular cholangiocarcinoma
- Prior multi-kinase inhibitor treatment for advanced disease
- Recent major or minor surgery within defined timeframes before randomization
- Recent anti-cancer agents, radiation therapy, or investigational therapy within specified washout periods
- Known brain or leptomeningeal metastases
- Known co-infection of hepatitis B and C viruses
- Active or history of certain autoimmune diseases or immune deficiencies with some exceptions
- History or evidence of active pneumonitis or certain lung diseases
- Other diseases or lab findings that contraindicate investigational drug use or increase risk
- Recent live, attenuated vaccine use or planned use during study treatment
- History of severe allergic reactions to similar antibodies or atezolizumab components
- Untreated or high-risk esophageal/gastric varices
- Recent use of systemic immunostimulatory or immunosuppressive medications with exceptions
- Treatment with strong CYP3A4 inducers or inhibitors within 14 days prior to randomization for cabozantinib patients
- Active tuberculosis or uncontrolled significant illnesses including cardiovascular disorders
- Known HIV infection with immunocompromised state excluded
- Prior allogenic stem cell or solid organ transplantation
- Uncontrolled pleural, pericardial effusion, or ascites requiring frequent drainage
- Uncontrolled or symptomatic hypercalcemia
- Uncontrolled tumor-related pain or symptomatic lesions needing prior treatment
- Other malignancies within 5 years except certain treated cancers
- Pregnancy, breastfeeding, or intention to become pregnant during or shortly after treatment
- Uncontrolled hepatic encephalopathy within 6 weeks prior to randomization
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for screening and enrollment
Duration - Repeated 21-day cycles until disease progression or unacceptable toxicity
Participants receive either atezolizumab intravenously every 21 days plus a daily oral multi-kinase inhibitor (cabozantinib or lenvatinib) or a daily oral multi-kinase inhibitor alone. Treatment cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Visits every 21 days for treatment administration and monitoring
Duration - Up to 2 years
After treatment ends, participants are monitored every 9 weeks for up to 2 years to assess long-term outcomes and safety.
Follow-up visits every 9 weeks
Trial Site Locations
Total: 16 locations
1
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
Actively Recruiting
2
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
Withdrawn
3
Cleveland Clinic Weston Florida
Weston, Florida, United States, 33331
Withdrawn
4
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Not Yet Recruiting
5
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, United States, 61801
Actively Recruiting
6
University Medical Center New Orleans
New Orleans, Louisiana, United States, 70112
Actively Recruiting
7
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, United States, 48106
Actively Recruiting
8
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Not Yet Recruiting
9
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Actively Recruiting
10
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Actively Recruiting
11
Duke University Medical Center
Durham, North Carolina, United States, 27710
Completed
12
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Withdrawn
13
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
Actively Recruiting
14
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57701
Actively Recruiting
15
Froedtert and the Medical College of Wisconsin LAPS
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
16
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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