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Hepatocellular Carcinoma (HCC)Phase 1NCT07075120

Ipilimumab and Nivolumab With SBRT in Locally Advanced Hepatocellular Cancer

A Phase 1 study testing Ipilimumab and Nivolumab and Stereotactic Body Radiotherapy (SBRT) in people with Hepatocellular Carcinoma (HCC), run by University of Hawaii at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, with Native Hawaiian and Pacific Islander (NHPI) populations experiencing significantly higher mortality rates compared to other groups in Hawaii. 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?
Ipilimumab and Nivolumab and Stereotactic Body Radiotherapy (SBRT)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
1 Apr 2026to 31 Dec 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Histologically or cytologically confirmed hepatocellular cancer
  • Locally advanced/borderline resectable HCC as defined by:
  • Solitary tumor >5 cm, OR
  • Unilobar multifocal disease either with >3 tumors or one tumor >3 cm, OR
  • Bilobar disease with adequate future liver remnant, still technically resectable, OR
  • High risk disease features (tumor >3 cm with macrovascular invasion or tumor >3 cm with AFP>400).
Show all 19Show fewer
  • No extrahepatic spread, no nodal disease, no bilateral left and right branch portal vein involvement, no hepatic vein / IVC involvement. Unilateral hepatic vein involvement is not exclusionary.
  • Measurable disease per RECIST 1.1 as determined by the investigator
  • Age ≥ 18 years old on the day of consent
  • ECOG performance status ≤1 (Appendix XX)
  • Adequate organ and marrow function, as defined below. Criteria "a," "b," "c," and "f" cannot be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose.
  • Hemoglobin ≥9 g/dL
  • Absolute neutrophil count ≥1000/μL
  • Platelet count ≥90,000/μL
  • Total bilirubin (TBL) <2.0 mg/dL
  • ASTandALT≤5×ULN
  • Albumin≥2.8g/dL
  • International normalized ratio(INR)≤2xULN
  • Calculated creatinine clearance ≥ 40 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance

Who cannot join

  • Prior systemic therapy for hepatocellular carcinoma
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug(s).
  • Ascites that requires ongoing paracentesis, within 6 weeks prior to the first scheduled dose, to control symptoms.
  • Active or prior documented GI variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 60 days prior to registration; adequate endoscopic therapy according to institutional standards is required for patients with history of esophageal variceal bleeding or assessed as high risk for esophageal variceal by the treating investigator.
  • Hepatic encephalopathy within 12 months of trial registration
  • Patient currently exhibits symptomatic or uncontrolled hypertension defined as diastolic blood pressure >90 mmHg or systolic blood pressure >140 mmHg.
Show all 16Show fewer
  • Prior external beam radiation therapy to the liver, prior yttrium-90 radioembolization
  • HBV viral load >100 IU/mL, ongoing corticosteroid therapy >10 mg prednisone daily, and active autoimmune disease requiring systemic therapy in the past 2 years.
  • Direct tumor extension into stomach, duodenum, small or large bowel
  • Active or untreated central nervous system (CNS) and leptomeningeal metastases
  • History of another primary malignancy except for:
  • Malignancy treated with curative intentand with no known active disease ≥ 5years before the first dose of study drug(s) and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • Active infection including tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), or human immunodeficiency virus (positive human HIV 1/2 antibodies).

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jared D Acoba, MD contact

8085318521

jacoba@hawaii.edu

Tomomi Otaki contact

8084404583

iit@cc.hawaii.edu

United States2 sites, 2 recruiting

  • The Queen's Medical Center

    Honolulu, Hawaii, 96813

    Jared Acoba, MD, 808-531-8521, jacoba@cc.hawaii.edu

    Recruiting

  • University of Hawai'i Cancer Center

    Honolulu, Hawaii, 96813

    Jared Acoba

    Jared Acoba

    Not yet recruiting

Other trials in United States

About this study

Official title: Pilot Study of Ipilimumab and Nivolumab With Response-adapted Stereotactic Body Radiotherapy Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Cancer

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, with Native Hawaiian and Pacific Islander (NHPI) populations experiencing significantly higher mortality rates compared to other groups in Hawaii. This disparity is influenced by factors such as higher prevalence of chronic hepatitis B, non-alcoholic fatty liver disease, limited access to early detection, and delayed diagnoses. NHPI patients are also underrepresented in clinical trials, limiting the relevance of treatment advances for this population.

The standard treatment for HCC is surgical resection; however, many NHPI patients present with unresectable disease. Recent advances with immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, have shown promise in treating advanced HCC and improving survival in previously untreatable cases. Additionally, stereotactic body radiotherapy (SBRT) has been shown to enhance survival and local control when combined with systemic therapies like ICIs. However, without surgery, outcomes remain suboptimal, with response rates for ICIs alone at 20-30%, and combination ICI-SBRT treatment showing slightly better results but still a high risk of progression.

Read more

Despite improvements in HCC treatment, significant gaps remain in managing borderline resectable disease, especially in NHPI patients. This study aims to evaluate the safety and efficacy of combining ICIs and SBRT with curative surgery for patients with borderline resectable HCC, focusing on NHPI populations. The study will also explore the use of biomarkers such as cell-free DNA (cfDNA), CD8+ T-cell infiltration, and serum cytokine markers to guide personalized treatment strategies. Preliminary findings suggest that this multimodal approach may improve outcomes and enable surgical resection for patients previously considered inoperable.

This study seeks to address the unmet need for effective treatment strategies in borderline resectable HCC and to improve survival outcomes for underserved NHPI populations.

Being tested
Ipilimumab and Nivolumab, Stereotactic Body Radiotherapy (SBRT)
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ipilimumab and NivolumabDrug

    Immunotherapy combination (Ipilimumab and Nivolumab) targeting CTLA-4 and PD-1 pathways to enhance immune response.

  • Stereotactic Body Radiotherapy (SBRT)Radiation

    High-dose radiation therapy delivered in 3-5 fractions for local control of tumors in combination with immunotherapy. Radiation dosages are based on the RTOG 1112 trial guidelines to minimize normal tissue exposure.

Study groups in NCT07075120
Study groupRoleWhat they receive
Ipilimumab and Nivolumab with SBRT and Surgical ResectionExperimentalArm A: Patients receive ipilimumab 3mg/kg and nivolumab 1mg/kg for nine weeks (three cycles). Following completion of preoperative immunotherapy, imaging with CT or MRI is performed to determine resectability. Eligible patients proceed to surgical resection. Arm B: Patients who are not eligible for resection continue immunotherapy (ipilimumab and nivolumab) for one additional cycle, then nivolumab 480mg every four weeks combined with stereotactic body radiotherapy (SBRT). SBRT is administered in 3-5 fractions, and patients continue imaging every nine weeks. Surgical resection is performed once resectability is confirmed.
Receives: Drug: Ipilimumab and Nivolumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of Treatment Regimen

    Feasibility will be defined as fewer than 5 failures of resection due to treatment-related factors (e.g., toxicity, delay in treatment).

    (Co-primary endpoint; this outcome assesses the tolerability and logistical feasibility of the neoadjuvant treatment strategy.) Unit of Measure: Number of failures (count)

    Measured: From treatment initiation to surgery completion (up to 12 months)

  2. R0 Resection Rate

    The proportion of patients achieving R0 surgical resection, defined as complete resection with negative margins.

    (Co-primary endpoint; this outcome reflects the treatment's impact on surgical resectability.) Unit of Measure: Percentage of participants

    Measured: From treatment initiation to surgery (up to 12 weeks)

Secondary outcomes (4)

  1. Objective Response Rate (ORR)

    ORR will be assessed based on RECIST v1.1 criteria.

    Measured: From the date of treatment initiation until the date of best documented response, assessed up to 36 months.

  2. Pathologic Complete Response (pCR) and Disease-Free Survival (DFS)

    pCR and DFS will be evaluated as secondary endpoints.

    Measured: From the date of treatment initiation until disease recurrence or progression, assessed up to 36 months.

  3. Overall Survival (OS)

    OS will be estimated from the date of treatment initiation to the date of death.

    Measured: From the date of treatment initiation until death, assessed up to 36 months.

  4. Toxicity Evaluation

    Toxicity will be evaluated using the CTCAE v6.0 grading system for grade 3-4 adverse events prior to surgery.

    Measured: From the start of treatment to the time of surgery, assessed up to 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2025
  2. Study start1 Apr 2026 (estimated)
  3. Primary completion1 Aug 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07075120
Sponsor's protocol ID
ACOBA-2024-1
Status last verified
Apr 2026
First submitted
20 Jun 2025
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chopra S, George K, Engineer R, Rajamanickam K, Nojin S, Joshi K, Swamidas J, Shetty N, Patkar S, Patil P, Ostwal V, Mehta S, Goel M. Stereotactic body radio therapy for inoperable large hepatocellular cancers: results from a clinical audit. Br J Radiol. 2019 Sep;92(1101):20181053. doi: 10.1259/bjr.20181053. Epub 2019 Jul 18.

    PubMed 31219706

  • Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, Davis JL, Hughes MS, Heller T, ElGindi M, Uppala A, Korangy F, Kleiner DE, Figg WD, Venzon D, Steinberg SM, Venkatesan AM, Krishnasamy V, Abi-Jaoudeh N, Levy E, Wood BJ, Greten TF. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017 Mar;66(3):545-551. doi: 10.1016/j.jhep.2016.10.029. Epub 2016 Nov 2.

    PubMed 27816492

  • Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, Melero I, Kudo M, Hou MM, Matilla A, Tovoli F, Knox JJ, Ruth He A, El-Rayes BF, Acosta-Rivera M, Lim HY, Neely J, Shen Y, Wisniewski T, Anderson J, Hsu C. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):e204564. doi: 10.1001/jamaoncol.2020.4564. Epub 2020 Nov 12.

    PubMed 33001135

  • Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

    PubMed 29875066

  • Li Z, Liu J, Zhang B, Yue J, Shi X, Cui K, Liu Z, Chang Z, Sun Z, Li M, Yang Y, Ma Z, Li L, Zhang C, Sun P, Zhong J, Zhao L. Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial. Nat Commun. 2024 Apr 16;15(1):3260. doi: 10.1038/s41467-024-47420-3.

    PubMed 38627377

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PubMed 32402160

  • Juloori A, Katipally RR, Lemons JM, Singh AK, Iyer R, Robbins JR, George B, Hall WA, Pitroda SP, Arif F, Fung J, Pillai A, Liao CY, Sharma M, Liauw SL. Phase 1 Randomized Trial of Stereotactic Body Radiation Therapy Followed by Nivolumab plus Ipilimumab or Nivolumab Alone in Advanced/Unresectable Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys. 2023 Jan 1;115(1):202-213. doi: 10.1016/j.ijrobp.2022.09.052. Epub 2022 Sep 13.

    PubMed 36108891

  • Luke JJ, Onderdonk BE, Bhave SR, Karrison T, Lemons JM, Chang P, Zha Y, Carll T, Krausz T, Huang L, Martinez C, Janisch LA, Hseu RD, Moroney JW, Patel JD, Khodarev NN, Salama JK, Ott PA, Fleming GF, Gajewski TF, Weichselbaum RR, Pitroda SP, Chmura SJ. Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Clin Cancer Res. 2020 Dec 15;26(24):6437-6444. doi: 10.1158/1078-0432.CCR-20-1790. Epub 2020 Oct 7.

    PubMed 33028595

  • Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, Al-Hallaq HA, Arina A, Khodarev NN, Janisch L, Chang P, Patel JD, Fleming GF, Moroney J, Sharma MR, White JR, Ratain MJ, Gajewski TF, Weichselbaum RR, Chmura SJ. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018 Jun 1;36(16):1611-1618. doi: 10.1200/JCO.2017.76.2229. Epub 2018 Feb 13.

    PubMed 29437535

  • Korpics MC, Polley MY, Bhave SR, Redler G, Pitroda SP, Luke JJ, Chmura SJ. A Validated T Cell Radiomics Score Is Associated With Clinical Outcomes Following Multisite SBRT and Pembrolizumab. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):189-195. doi: 10.1016/j.ijrobp.2020.06.026. Epub 2020 Jun 20.

    PubMed 32569799

  • Onderdonk BE, Chmura SJ. The Yin and Yang of Cytoreductive SBRT in Oligometastases and Beyond. Front Oncol. 2019 Aug 2;9:706. doi: 10.3389/fonc.2019.00706. eCollection 2019.

    PubMed 31428580

  • Dawson LA, Winter KA, Knox JJ, Zhu AX, Krishnan S, Guha C, Kachnic LA, Gillin MT, Hong TS, Craig TD, Williams TM, Hosni A, Chen E, Noonan AM, Koay EJ, Sinha R, Lock MI, Ohri N, Dorth JA, Delouya G, Swaminath A, Moughan J, Crane CH. Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2025 Feb 1;11(2):136-144. doi: 10.1001/jamaoncol.2024.5403.

    PubMed 39699905

  • Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN, Rimassa L, Breder V, Vasilyev A, Heurgue A, Tam VC, Mody K, Thungappa SC, Ostapenko Y, Yau T, Azevedo S, Varela M, Cheng AL, Qin S, Galle PR, Ali S, Marcovitz M, Makowsky M, He P, Kurland JF, Negro A, Sangro B. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070. doi: 10.1056/EVIDoa2100070. Epub 2022 Jun 6.

    PubMed 38319892

  • Guo A, Pomenti S, Wattacheril J. Health Disparities in Screening, Diagnosis, and Treatment of Hepatocellular Carcinoma. Clin Liver Dis (Hoboken). 2021 Jun 4;17(5):353-358. doi: 10.1002/cld.1057. eCollection 2021 May. No abstract available.

    PubMed 34136141

  • Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):589-604. doi: 10.1038/s41575-019-0186-y. Epub 2019 Aug 22.

    PubMed 31439937

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab and Nivolumab and Stereotactic Body Radiotherapy (SBRT) in people with Hepatocellular Carcinoma (HCC), run by University of Hawaii at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jared D Acoba, MD (8085318521, jacoba@hawaii.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of Treatment Regimen (time frame: From treatment initiation to surgery completion (up to 12 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07075120, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

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