Ipilimumab and Nivolumab With SBRT in Locally Advanced Hepatocellular Cancer

NCT07075120 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ACOBA-2024-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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. 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. 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.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (2)

• 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)

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

• 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

  From treatment initiation to surgery (up to 12 weeks)

Secondary Outcomes (4)

• Objective Response Rate (ORR)

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

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

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

• Overall Survival (OS)

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

• Toxicity Evaluation

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

Study Arms (1)

Ipilimumab and Nivolumab with SBRT and Surgical Resection

EXPERIMENTAL

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.

Drug: Ipilimumab and Nivolumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

Ipilimumab and Nivolumab DRUG

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

Ipilimumab and Nivolumab with SBRT and Surgical Resection

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.

Ipilimumab and Nivolumab with SBRT and Surgical Resection

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
• 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).
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Hawaii: lead

Study Sites (2)

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

RECRUITING

University of Hawai'i Cancer Center

Honolulu, Hawaii, 96813, United States

NOT YET RECRUITING

Related Publications (15)

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Related Links

• 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.

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Ipilimumab; Nivolumab; Radiosurgery

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jared D Acoba, MD

  University of Hawaii

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jared D Acoba, MD

CONTACT

8085318521; jacoba@hawaii.edu

Tomomi Otaki

CONTACT

8084404583; iit@cc.hawaii.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: July 20, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)