Ipilimumab and Nivolumab With SBRT in Locally Advanced Hepatocellular Cancer
ConditionHepatocellular Carcinoma (HCC)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Hawaii
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed hepatocellular cancer
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
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Ipilimumab and Nivolumab
DrugImmunotherapy combination (Ipilimumab and Nivolumab) targeting CTLA-4 and PD-1 pathways to enhance immune response.
Stereotactic Body Radiotherapy (SBRT)
RadiationHigh-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.
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: Ipilimumab and Nivolumab with SBRT and Surgical ResectionExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
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)
Time frame
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
Time frame
From treatment initiation to surgery (up to 12 weeks)Secondary outcomes
1
Objective Response Rate (ORR)
ORR will be assessed based on RECIST v1.1 criteria.
Time frame
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.
Time frame
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.
Time frame
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.
Time frame
From the start of treatment to the time of surgery, assessed up to 12 months.Sponsors and contacts
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Source ClinicalTrials.gov