Repurposing Celecoxib to Overcome Resistance to Immunotherapy in Advanced HCC (RECON Study)
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%)
• Platelet count \> 100,000 cells/ ul (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Hemoglobin (Hb) \> 9g/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Absolute neutrophil count \> 1000 cells/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Albumin \> 3g/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Total bilirubin \< 3mg/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Glomerular filtration rate (GFR) \> 60ml/min (based on creatine, and cystatin C estimation where applicable) (within 28 days of cycle 1 day 1, at the discretion of the investigator)
• Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
• FCBP and men treated or enrolled on this protocol 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 3 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• \* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Completion of all previous cancer directed therapy (including, radiotherapy, liver lesion ablation, bland or chemoembolization and transarterial radioembolization therapy) ≥ 4 weeks before the start of study therapy.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better.
‣ Patients without existing cardiac disease that could raise the risk of complications who consent for the trial will proceed with trial participation
⁃ Patients with existing cardiac disease that could raise the risk of complications will be referred at the discretion of the investigator to a cardio-oncologist or general cardiologist for cardiac optimization prior to starting celecoxib
• Life expectancy \> 12 weeks as determined by the investigator
• Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. This includes willingness to undergo mandatory blood sample draws for evaluation of correlatives
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.