Ipilimumab and nivolumab plus focused liver radiation for locally advanced liver cancer

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

This trial tests whether combining nivolumab and ipilimumab with focused liver radiation (SBRT) can help adults with locally advanced hepatocellular carcinoma, with attention to including Native Hawaiian and Pacific Islander patients.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Hawaii (other)
• Drugs / interventions: radiation, prednisone, nivolumab, ipilimumab
• Locations: 2 sites (Honolulu, Hawaii and 1 other locations)
• Trial ID: NCT07075120 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label interventional study combines two immune checkpoint inhibitors—nivolumab and ipilimumab—with stereotactic body radiotherapy (SBRT) to treat adults with locally advanced or borderline resectable hepatocellular carcinoma. Participants must have measurable liver tumors without extrahepatic spread and meet criteria including ECOG 0–1 and adequate organ and marrow function. The primary focus is safety and tolerability of the combination and determining a recommended dose and schedule, with secondary observation of tumor response by RECIST 1.1 and local control after SBRT. Enrollment is conducted at The Queen's Medical Center and the University of Hawai'i Cancer Center with emphasis on including Native Hawaiian and Pacific Islander patients to address local disparities.

Who should consider this trial

Good fit: Adults (≥18) with histologically or cytologically confirmed locally advanced or borderline resectable HCC, measurable disease by RECIST 1.1, ECOG ≤1, no extrahepatic spread, and adequate organ function.

Not a fit: Patients with extrahepatic metastatic disease, widespread nodal involvement, poor performance status, or inadequate liver/organ function are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could improve local tumor control and increase the chance of converting unresectable tumors to resectable disease, potentially prolonging survival.

How similar studies have performed: Prior studies have shown activity of nivolumab and ipilimumab in advanced HCC, and early research combining immune checkpoint inhibitors with radiotherapy is promising but not yet definitive.

Eligibility criteria

Main Criteria for Inclusion/Exclusion

* Inclusion Criteria:

  * 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).
  * 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:

  * 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.
  * 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).

Where this trial is running

Honolulu, Hawaii and 1 other locations

• The Queen's Medical Center — Honolulu, Hawaii, United States (RECRUITING)
• University of Hawai'i Cancer Center — Honolulu, Hawaii, United States (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Jared D Acoba, MD — University of Hawaii
• Study coordinator: Jared D Acoba, MD

Conditions: Hepatocellular Carcinoma