Hepatocellular Carcinoma (HCC)Phase 2NCT07689175
Adaptive Dosing of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma
A Phase 2 study testing Nivolumab and Ipilimumab (3 mg/kg) in people with Hepatocellular Carcinoma (HCC), run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if immunotherapy including nivolumab plus ipilimumab is effective and safe in treating hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Nivolumab and Ipilimumab (3 mg/kg)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2026to 31 Oct 2032
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC or combined HCC-cholangiocarcinoma will be excluded.
- Patients may not have received any prior anti-PD-1/L1 or anti-CTLA-4 therapies for the treatment of advanced HCC.
- Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
- Child-Pugh Score B7-8
- Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST v.1.1.
- Prior locoregional therapy is allowed provided the target lesion has increased in size ≥25% since the cessation of locoregional therapy or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion.
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- Age ≥ 18 years.
- ECOG performance score 0-2
- Adequate organ and marrow function as defined below:
- Platelet count ≥ 40,000/mm3
- Hgb ≥ 8 g/dl
- INR ≤ 2
- AST, ALT ≤ 5 times ULN
- Calculated creatinine clearance (CrCl) ≥ 35 mL/min. CrCl can be calculated using the Cockcroft-Gault method.
- Albumin ≥ 2.0 g/dl
- All men, as well as women of child-bearing potential 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 for 120 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- 10a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- 11. Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Prior solid organ transplant.
- Hypersensitivity to IV contrast; not suitable for pre-medication.
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- Active autoimmune disease that requires current systemic treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for conditions that, in the investigator's opinion, do not have a substantial hazardous risk such as asthma, and cutaneous and musculoskeletal rheumatologic conditions.
- Known human immunodeficiency virus infection (testing not required) in a patient not on antiretroviral therapy and detectable viral load.
- Prior malignancy that required systemic treatment within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Preneoplastic or malignant diagnoses that are indolent in nature and do not require active systemic treatment are not excluded.
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- If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if:
- Has evidence of progression by neurologic symptoms
- Has metastatic brain lesions that require immediate intervention.
- Has carcinomatous meningitis, regardless of clinical stability
- Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
- Uncontrolled intercurrent 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, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- Prisoners or subjects who are involuntarily incarcerated.
- Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Carrie Manwaring, BS, 214-648-7097, carrie.manwaring@utsouthwestern.edu
David Hsieh, MD
About this study
Official title: Phase 2 Trial of Adaptive Dosing of Immune Checkpoint Inhibitors for Unresectable Child Pugh B Hepatocellular Carcinoma
The goal of this clinical trial is to learn if immunotherapy including nivolumab plus ipilimumab is effective and safe in treating hepatocellular carcinoma.
Read the detailed description
This clinical trial will examine an adaptive dosing strategy for patients with Child-Pugh B disease and HCC in which immunotherapy doses will be interrupted for a short-interval restaging exam for patients who have achieved a favorable radiographic response. If disease response or control is sustained at this early interim imaging assessment, subsequent treatment management is up to the treating investigator discretion. Treatment may be resumed if the investigator judges that continued therapy is likely to provide additional clinical benefit. Alternatively, treatment may be further held or discontinued if continued therapy is unlikely to confer meaningful benefit and the potential risks of cumulative immune-related toxicity or hepatic decompensation outweigh the anticipated benefit of ongoing treatment. If disease progression is detected at the short-interval staging scan, subsequent line treatment will be administered per investigator discretion in accordance with institutional standards of care and patient clinical status. For patients who do not achieve a favorable response at the first initial assessment, immunotherapy will be continued until a favorable response is reached or until progression.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Nivolumab, Ipilimumab (3 mg/kg)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Nivolumab 1 mg/kg every 3 weeks for a maximum of 4 doses as part of combination therapy; then 240 mg every 2 weeks or 480 mg every 4 weeks as single agent.
Ipilimumab (3 mg/kg)Drug
ipilimumab 3 mg/kg for a maximum of 4 doses as part of combination therapy, for a maximum of 4 doses.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab plus ipilimumab | Experimental | Administration:
* Route: Intravenous (IV) infusion only.
* Schedule and Dose:
* Cycles 1-4:
Nivolumab 1 mg/kg IV every 3 weeks Ipilimumab 3 mg/kg mg IV every 3 weeks
o Subsequent cycles: Nivolumab 480 mg IV every 4 weeks Receives: Drug: Nivolumab; Drug: Ipilimumab (3 mg/kg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease control rate after immunotherapy nivolumab plus ipilimumab
To determine the proportion of patients with imaging evidence of subsequent disease control (stable disease, partial response, or complete response); Per RECIST v.1.1. among subjects who attained an initial favorable imaging response.
Measured: From time of initial treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Secondary outcomes (6)
Overall response rate of combination nivolumab plus ipilimumab
To determine the overall response rate of combination immunotherapy nivolumab plus ipilimumab based on Investigator assessment, per RECIST v.1.1.
Measured: Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Favorable response rate combination immunotherapy nivolumab plus ipilimumab
To determine the favorable response rate of combination immunotherapy nivolumab plus ipilimumab based on Investigator assessment, per RECIST v.1.1.
Measured: Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Objective response rate of combination immunotherapy nivolumab plus ipilimumab
To determine the objective response rate (ORR) of combination immunotherapy nivolumab plus ipilimumab. The objective response rate is defined as the rate of CR + PR as the best response on evaluation; measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measured: Initial treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Progression-free survival of combination immunotherapy nivolumab plus ipilimumab
To determine the progression-free survival rate of response of immunotherapy nivolumab plus ipilimumab assessed by RECIST guidelines (version 1.1)
Measured: Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Overall survival to immunotherapy nivolumab plus ipilimumab
To determine the overall survival rate of response of combination nivolumab plus ipilimumab assessed by RECIST guidelines (version 1.1)
Measured: Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Number of participants with Adverse Events (AEs) (serious / non-serious) as defined by CTCAE v5.0
Safety profile of combination nivolumab plus ipilimumab will be measured by the number of participants with Adverse Events (AEs) (serious / non-serious) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start21 Aug 2026
- Primary completion31 Oct 2031 (estimated)
- Study completion31 Oct 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, David Hsieh, University of Texas Southwestern Medical Center
- Investigators
- David Hsieh, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07689175
- Sponsor's protocol ID
- STU20261069
- Status last verified
- Aug 2026
- First submitted
- 30 Jun 2026
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No