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

NCT ID: NCT07174570

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-28

Study Completion Date

2027-11-13

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate the efficacy of the combination of celecoxib, and durvalumab+ tremelimumab in advanced hepatocellular carcinoma (HCC).

SECONDARY OBJECTIVES:

I. To evaluate the activity of the combination of celecoxib, and durvalumab+ tremelimumab in advanced HCC.

II. To evaluate the safety and feasibility of the combination of celecoxib, and durvalumab+ tremelimumab in advanced HCC.

TERTIARY/EXPLORATORY:

I. To evaluate biomarkers associated with the efficacy of the combination of celecoxib, and durvalumab+ tremelimumab in advanced HCC.

OUTLINE:

Patients receive celecoxib orally (PO) twice daily (BID) on days 1-28 of each cycle, durvalumab intravenously (IV) over 30-60 minutes on day 1 of each cycle and tremelimumab IV over 30-60 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, computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients may undergo tissue biopsy during screening.

After completion of study treatment, patients are followed up at 30 days, and then every 12 weeks for up to 2 years.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (celecoxib, durvalumab, tremelimumab)

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.

Group Type EXPERIMENTAL

Celecoxib

Intervention Type DRUG

Receive by mouth (PO).

Durvalumab

Intervention Type BIOLOGICAL

Receive intravenously (IV).

Tremelimumab

Intervention Type BIOLOGICAL

Given intravenously (IV).

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo Computed Tomography (CT).

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo Magnetic Resonance Imaging (MRI).

Biopsy Procedure

Intervention Type PROCEDURE

Undergo tissue biopsy.

Interventions

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Celecoxib

Receive by mouth (PO).

Intervention Type DRUG

Durvalumab

Receive intravenously (IV).

Intervention Type BIOLOGICAL

Tremelimumab

Given intravenously (IV).

Intervention Type BIOLOGICAL

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo Computed Tomography (CT).

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo Magnetic Resonance Imaging (MRI).

Intervention Type PROCEDURE

Biopsy Procedure

Undergo tissue biopsy.

Intervention Type PROCEDURE

Other Intervention Names

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, 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 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) 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, Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection 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 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 Biopsy, BIOPSY, Biopsy, Biopsy, Biopsy, biopsy, Biopsy, Biopsy, Biopsy, Biopsy, Biopsy, BIOPSY_TYPE, BIOPSY_TYPE, BIOPSY_TYPE, Bx

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Olumide Gbolahan

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Olumide B. Gbolahan, MBBS, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Grady Health System

Atlanta, Georgia, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status

Countries

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United States

Central Contacts

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Olumide B. Gbolahan, MBBS, MSc

Role: CONTACT

404-778-1900

Facility Contacts

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Kathleen Coleman

Role: primary

404-251-1278

Kathleen Coleman

Role: primary

404-251-1278

Kathleen Coleman

Role: primary

404-251-1278

Kathleen Coleman

Role: primary

404-251-1278

Other Identifiers

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P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-06192

Identifier Type: REGISTRY

Identifier Source: secondary_id

WINSHIP6414-24

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00008622

Identifier Type: -

Identifier Source: org_study_id

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