PULSAR Radiotherapy Combined With Immunotherapy for High-Risk Advanced Liver Cancer

NCT07884877 | Recruiting Phase 2

• 1 other identifier: SMC 2026-07-217
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if adding PULSAR, a personalized adaptive stereotactic radiotherapy, to standard immunotherapy can control cancer longer in adults with high-risk advanced hepatocellular carcinoma (liver cancer). It will also learn about the safety of this combination. The main questions it aims to answer are:

• What percentage of participants are alive without cancer progression 12 months after starting PULSAR?
• What medical problems do participants have after PULSAR with immunotherapy? There is no comparison group. Results will be compared with published results of immunotherapy alone. Participants will:
• Continue their usual immunotherapy
• Receive 2 to 3 PULSAR sessions, 3 to 4 weeks apart, with the plan adjusted before each session
• Give blood samples and fill out symptom questionnaires
• Have checkups and scans for up to 3 years

Conditions

Hepatocellular Carcinoma (HCC); Radiotherapy-Induced Immune Priming; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 12-Month Progression-Free Survival Rate

  Proportion of participants alive without progression (RECIST v1.1) or death at 12 months from the start of radiotherapy, estimated by the Kaplan-Meier method.

  12 months from start of radiotherapy

Secondary Outcomes (7)

• Progression-Free Survival

  Up to 36 months

• 6-Month Progression-Free Survival Rate

  6 months from start of radiotherapy

• Objective Response Rate

  Up to 36 months

• Overall Survival

  Up to 36 months

• Disease Control Rate

  Up to 36 months

Other Outcomes (3)

• Change in Peripheral Immune Cell Subsets and Plasma Cytokines

  Before each pulse and 3 months after radiotherapy

• Change in CT Radiomic Features

  Before each pulse

• Patient-Reported Adverse Events (PRO-CTCAE)

  Baseline through 36 months

Study Arms (1)

PULSAR Plus Immunotherapy

EXPERIMENTAL

Participants continue standard-of-care immune checkpoint inhibitor-based therapy (e.g., atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab) and receive PULSAR (photon or proton), 8-12 Gy per pulse, 2-3 pulses at 3- to 4-week intervals between immunotherapy cycles, with CT-based adaptive re-planning before each pulse.

Radiation: PULSAR (Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy); Drug: Immune checkpoint inhibitor-based therapy

Interventions

Immune checkpoint inhibitor-based therapy DRUG

Standard-of-care immune checkpoint inhibitor-based systemic therapy chosen by the treating physician. Not provided by the study.

Also known as: Atezolizumab plus bevacizumab, Durvalumab plus tremelimumab, Nivolumab

PULSAR Plus Immunotherapy

PULSAR (Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy) RADIATION

Stereotactic radiotherapy (photon or proton), 8-12 Gy per pulse, 2-3 pulses at 3- to 4-week intervals, delivered between immunotherapy cycles. CT-based adaptive re-planning is performed before each pulse, with target volume reduced according to tumor response.

Also known as: Pulsed stereotactic adaptive radiotherapy

PULSAR Plus Immunotherapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19 years or older
• Hepatocellular carcinoma diagnosed histologically or clinically according to the Korean Liver Cancer Association-National Cancer Center guidelines
• Unresectable and/or locally advanced or metastatic disease, currently receiving or scheduled to receive immune checkpoint inhibitor-based systemic therapy (e.g., atezolizumab plus bevacizumab or durvalumab plus tremelimumab)
• At least one of the following high-risk features:
• Tumor larger than 5 cm in maximum diameter
• Portal vein tumor thrombosis (Vp2-4)
• Infiltrative lesion
• Bile duct invasion
• Inferior vena cava invasion
• Extrahepatic metastasis
• At least one measurable target lesion per RECIST version 1.1, with PULSAR already planned by the treating physician
• ECOG performance status 0-1
• Child-Pugh score 7 or lower
• Known hepatitis B and C virus status, with antiviral therapy per institutional policy if indicated
• Voluntary written informed consent

You may not qualify if:

• Pregnant or breastfeeding women
• Active brain or leptomeningeal metastases
• More than 5 extrahepatic metastatic lesions (multiple intrahepatic lesions are allowed)
• Prior radiotherapy to the treatment site
• Moderate or refractory ascites, or hepatic encephalopathy
• Contraindications to immune checkpoint inhibitors, such as active autoimmune disease requiring systemic treatment (hypothyroidism stable on hormone replacement and type 1 diabetes controlled with insulin are allowed)
• Uncontrolled serious comorbidities (e.g., uncontrolled infection, NYHA class II or higher heart disease, myocardial infarction or stroke within 3 months, unstable angina or arrhythmia)
• Unable to comply with the study protocol
• Considered unsuitable for the study by the investigator

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung medical center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

DEAE-Dextran; atezolizumab; Bevacizumab; durvalumab; tremelimumab; Nivolumab

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)

Dextrans; Glucans; Polysaccharides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Nalee Kim, MD, PhD

CONTACT

82-2-3410-2612; rodr.naleekim@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: October 13, 2026
• First Posted: October 21, 2026
• Study Start: October 15, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2030
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)