Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer
A Phase II Randomized Study of Atezolizumab Plus Multi-Kinase Inhibitor Versus Multi-Kinase Inhibitor Alone in Subjects With Unresectable, Advanced Hepatocellular Carcinoma Who Previously Received Atezolizumab Plus Bevacizumab
3 other identifiers
interventional
122
1 country
16
Brief Summary
This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2022
Typical duration for phase_2
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 8, 2021
CompletedFirst Posted
Study publicly available on registry
December 23, 2021
CompletedStudy Start
First participant enrolled
May 27, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
ExpectedSeptember 16, 2025
September 1, 2025
3.6 years
December 8, 2021
September 10, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Overall survival (OS)
The final analysis for OS will be conducted when 84 OS events are observed, approximately 36 months after first subject in and will be evaluated with a one-sided p-value from stratified log-rank test.
From randomization to death from any cause, assessed up to 3 years
Progression-free survival (PFS)
PFS analysis will be conducted when 89 PFS events are observed. The one-sided p-value from stratified log-rank test will be used for decision making.
From randomization to first documentation of disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or death, assessed up to 2 years
Secondary Outcomes (3)
Objective response rate (ORR)
Up to 2 years
Duration of response
Up to 2 years
Incidence of adverse events (AEs)
Up to 30 days after last dose
Study Arms (2)
Arm A (atezolizumab, cabozantinib or lenvatinib)
EXPERIMENTALPatients receive atezolizumab IV over 30-60 minutes on day 1 and cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm B (cabozantinib or lenvatinib)
ACTIVE COMPARATORPatients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Provide written informed consent =\< 28 days prior to randomization
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- NOTE: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up
- Age \>= 18 years
- Hepatocellular carcinoma (HCC) confirmed by histological/cytological diagnosis or clinically per the American Association for the Study of Liver Diseases (AASLD) or WASL 2018 criteria
- Locally advanced, metastatic and/or unresectable disease that is not amendable to curative treatment
- Previously progressed on atezolizumab in combination with bevacizumab as first line systemic therapy for advanced disease
- NOTE: 2nd line patients only
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Child Pugh class A
- Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) serology tests.
- For subjects with active HBV, HBV deoxyribonucleic acid (DNA) \< 500 IU/mL obtained ≤ =\< 28 days prior to randomization, and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study
- At least one measurable untreated malignant lesion per RECIST v1.1. Subjects who previously received local therapy (e.g., ablation, percutaneous ethanol injection, trans-arterial embolization/chemo-embolization) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1
- Consent to using archival tumor tissues, if available
- NOTE: Non-availability of tumor tissue does not exclude the subject.
- +17 more criteria
You may not qualify if:
- Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma
- Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)
- NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed \>= 6 months prior to randomization
- Any of the following prior therapies:
- Major surgery =\< 4 weeks prior to randomization; Minor surgery =\< 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion of central lines/Mediport). Subjects with clinically relevant complications from prior surgery are not eligible
- Any anti-cancer agent =\< 2 weeks prior to randomization
- Radiation therapy =\< 4 weeks (1 week for palliative radiation for bone metastases and/or for pain control) or radionuclide treatment (e.g., I-131 or Y-90) =\< 6 weeks prior to randomization
- Treatment with investigational therapy =\< 28 days prior to randomization
- Known brain or leptomeningeal metastasis
- Known co-infection of HBV and HCV. Subjects with a history of HCV infection but who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) will be considered non-infected with HCV
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
- Subjects with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
- Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
- Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
- Rash must cover \< 10% of body surface area
- +37 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Academic and Community Cancer Research Unitedlead
- National Cancer Institute (NCI)collaborator
- Genentech, Inc.collaborator
Study Sites (16)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Cleveland Clinic Weston Florida
Weston, Florida, 33331, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, 61801, United States
University Medical Center New Orleans
New Orleans, Louisiana, 70112, United States
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, 48106, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
Rapid City Regional Hospital
Rapid City, South Dakota, 57701, United States
Froedtert and the Medical College of Wisconsin LAPS
Milwaukee, Wisconsin, 53226, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Wen Wee Ma
Academic and Community Cancer Research United
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2021
First Posted
December 23, 2021
Study Start
May 27, 2022
Primary Completion
December 31, 2025
Study Completion (Estimated)
December 31, 2026
Last Updated
September 16, 2025
Record last verified: 2025-09