This phase II trial tests how well the combination of celecoxib with durvalaumab and tremellimumab works in treating patients with hepatocellular cancer (liver cancer) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents and is used to reduces pain. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving celecoxib with durvalaumab and tremellimumab may better treat patients with advanced or metastatic liver cancer.
Histologically or cytologically confirmed hepatocellular cancer (HCC) planned for treatment at gastrointestinal clinics of Emory University's Winship Cancer Institute or Grady Cancer Center
Radiologically measurable disease based on Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Mild to moderate liver dysfunction evidenced by Child Pugh score 7B and above
History of arterial or venous thromboembolic events or gastrointestinal bleeding event. Subjects with portal venous thrombosis are permitted in the study if their treating oncologist does not deem it necessary to treat this with heparin products or direct acting anticoagulant (DOAC)
Current use of warfarin, heparin products and DOACs
Subjects with a history of (non-bleeding) peptic ulcer disease who have been on a proton pump inhibitor for less than 30 days prior to screening visit
Single group
Celecoxib
DrugReceive by mouth (PO).
Durvalumab
Biological/VaccineReceive intravenously (IV).
Tremelimumab
Biological/VaccineGiven intravenously (IV).
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo Computed Tomography (CT).
Magnetic Resonance Imaging
Procedure/SurgeryUndergo Magnetic Resonance Imaging (MRI).
Biopsy Procedure
Procedure/SurgeryUndergo tissue biopsy.
Progression-Free Survival (PFS)
PFS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median PFS will be estimated using the Brookmeyer-Crowley approach.
Objective Response Rate (ORR)
ORR defined as the proportion of all subjects whose best overall response is either a complete response or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 criteria. ORR will be reported as a proportion, and 95% exact binomial confidence interval will be estimated using the Clopper-Pearson method.
Incidence of Adverse Events (AE)
Will be determined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. Frequencies and percentages will be used to summarize safety events.
One Treatment Cycle
Frequencies and percentages will be used to determine the proportion of subjects who complete one treatment cycle.
Incidence of Adverse Events Profile
Incidence of Adverse Events (AE) profile with the combination of celecoxib, and durvalumab+ tremelumumab will be determined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. Frequencies and percentages will be used to summarize events.
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
