Celecoxib, Durvalumab and Tremelimumab for the Treatment of Patients With Advanced or Metastatic Liver Cancer

NCT07174570 | Recruiting Phase 2 FDA Drug

• 4 other identifiers: STUDY00008622P30CA138292NCI-2025-06192WINSHIP6414-24
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Metastatic Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Time between the date of registration and the first date of documented progression, regardless of discontinuation of study drug, or death due to any cause, whichever occurs first, assessed up to 2 years

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 2 years

• Incidence of Adverse Events (AE)

  Up to 2 years

• One Treatment Cycle

  During cycle 1 (cycle 1 = 28 days)

• Incidence of Adverse Events Profile

  Up to 2 years

Study Arms (1)

Treatment (celecoxib, durvalumab, tremelimumab)

EXPERIMENTAL

Patients receive celecoxib PO BID on days 1-28 of each cycle, durvalumab IV over 30 minutes on day 1 of each cycle and tremelimumab IV over 30 minutes on day 1 of cycle 1 only. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT or MRI throughout the study. Patients may undergo tissue biopsy during screening.

Drug: Celecoxib; Biological: Durvalumab; Biological: Tremelimumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biopsy Procedure

Interventions

Celecoxib DRUG

Receive by mouth (PO).

Also known as: , Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-,, Celecoxib, celecoxib, Elyxyb, Onsenal, SC-58635, YM 177, Celebrex, Celecoxib, CELECOXIB, CELECOXIB, 169590-42-5, 4-(5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide

Treatment (celecoxib, durvalumab, tremelimumab)

Durvalumab BIOLOGICAL

Receive intravenously (IV).

Also known as: Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736, 1428935-60-7, DURVALUMAB, Durvalumab, Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain)

Treatment (celecoxib, durvalumab, tremelimumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

Treatment (celecoxib, durvalumab, tremelimumab)

Computed Tomography PROCEDURE

Undergo Computed Tomography (CT).

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computed Tomography,Computed Tomography, Computerized axial tomography, Computerized Axial Tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT SCAN, CT scan, Diagnostic CAT Scan Service Type, tomography

Treatment (celecoxib, durvalumab, tremelimumab)

Magnetic Resonance Imaging PROCEDURE

Undergo Magnetic Resonance Imaging (MRI).

Also known as: Magnetic Resonance, Magnetic Resonance Imaging, MR, MR Imaging, MRI Scan, MRI, NMR Imaging, NMRI, nuclear magnetic resonance imaging,, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (celecoxib, durvalumab, tremelimumab)

Biopsy Procedure PROCEDURE

Undergo tissue biopsy.

Also known as: Biopsy, BIOPSY, Biopsy, Biopsy, Biopsy, biopsy, Biopsy, Biopsy, Biopsy, Biopsy, Biopsy, BIOPSY_TYPE, BIOPSY_TYPE, BIOPSY_TYPE, Bx

Treatment (celecoxib, durvalumab, tremelimumab)

Tremelimumab BIOLOGICAL

Given intravenously (IV).

Also known as: CP675206, Imjudo, Immunoglobulin G2, Anti-(Human CTLA-4 (Antigen)) (Human Monoclonal CP-675206 Clone 11.2.1 Heavy Chain) Disulfide with, 745013-59-6, Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206, CP-675, CP-675,206, CP-675206, CP675,

Treatment (celecoxib, durvalumab, tremelimumab)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• Patients who have had immune checkpoint inhibitors (ICI) therapy within 6 months prior to entering the study or those who have not recovered from adverse events due to liver directed therapy administered more than 4 weeks earlier (i.e., have residual toxicities \> grade 2)
• Patients who are receiving any other investigational agents or an investigational device within 28 days before administration of first dose of study drugs
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study
• Contraindication to ICI per investigator discretion
• Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolled grade ≥ 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite antihypertensive therapy
• Contraindication to non-steroidal anti-inflammatory drugs (NSAIDs): cardiac conditions that significantly raise the risk of cardiopulmonary complications, including unstable angina, uncontrolled heart failure, recent gastrointestinal (GI) bleed. Note that patients who are stable on low dose aspirin (\< 325mg/day) only will be allowed on study
• Current use of other NSAIDs.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Grady Health System

Atlanta, Georgia, 30303, United States

NOT YET RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Celecoxib; durvalumab; Disulfides; Immunoglobulin G; tremelimumab; Antigens; Specimen Handling; Magnetic Resonance Spectroscopy; Biopsy

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)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Factors; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Olumide B. Gbolahan, MBBS, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olumide B. Gbolahan, MBBS, MSc

CONTACT

404-778-1900; ogbolah@emory.edu

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: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 16, 2025
• Study Start: January 2, 2026
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): November 13, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (4)