Ipilimumab and Nivolumab With SBRT in Locally Advanced Hepatocellular Cancer
NCT ID: NCT07075120
Last Updated: 2025-10-28
Study Results
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Basic Information
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NOT_YET_RECRUITING
PHASE1
15 participants
INTERVENTIONAL
2025-12-01
2027-12-31
Brief Summary
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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.
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.
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Ipilimumab and Nivolumab with SBRT and Surgical Resection
Arm 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.
Ipilimumab and Nivolumab
Immunotherapy combination (Ipilimumab and Nivolumab) targeting CTLA-4 and PD-1 pathways to enhance immune response.
Stereotactic Body Radiotherapy (SBRT)
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.
Interventions
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Ipilimumab and Nivolumab
Immunotherapy combination (Ipilimumab and Nivolumab) targeting CTLA-4 and PD-1 pathways to enhance immune response.
Stereotactic Body Radiotherapy (SBRT)
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.
Eligibility Criteria
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Inclusion Criteria
* 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).
* 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
Exclusion Criteria
* 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.
* 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).
18 Years
ALL
No
Sponsors
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University of Hawaii
OTHER
Responsible Party
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Principal Investigators
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Jared D Acoba, MD
Role: PRINCIPAL_INVESTIGATOR
University of Hawaii
Locations
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University of Hawai'i Cancer Center
Honolulu, Hawaii, United States
Countries
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Central Contacts
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Facility Contacts
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Jared Acoba
Role: primary
References
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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.
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Related Links
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Hawai'i Tumor Registry: Cancer at a Glance 2014-2018, a summary of statewide cancer incidence and mortality data used to support regional relevance of the study.
Other Identifiers
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ACOBA-2024-1
Identifier Type: -
Identifier Source: org_study_id
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