Evaluation of Immune Responses and Outcomes in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy

Prospective Evaluation of Immune Responses and Outcomes in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy

Radiation therapy is a highly effective modality for managing localized solid tumors and has become a fundamental component of treating unresectable hepatocellular carcinoma. Our previous preclinical investigation revealed that radiotherapy can initiate immunogenic cell death and facilitate the cross-presentation of tumor antigens by antigen-presenting cells, thereby augmenting systemic anti-tumor T cell responses in murine tumor models. However, this immune response subsequent to irradiation has not been comprehensively evaluated in clinical trials involving hepatocellular carcinoma patients. Given that radiotherapy represents a standard therapeutic approach for unresectable hepatocellular carcinoma, our ongoing phase II non-randomized trial aims to prospectively assess immunological responses and dose-volumetric parameters, while identifying predictors of clinical outcomes in patients undergoing definitive radiotherapy for hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Photon or proton radiotherapy

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Rodney Cheng-En Hsieh, MD, PhD; Phone Number: 7000 +886-3-3281200; Email: chsieh@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital at Linkou
    • Contact: Rodney Cheng-En Hsieh, MD, PhD; Phone Number: 7000 +88633281200; Email: rodney445@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients undergoing routine radiotherapy using photons or protons for HCC

Description

Inclusion Criteria:

1. Participants must have diagnosis of HCC. Participants may have multiple lesions. Diagnosis should be confirmed by at least 1 criteria listed below:

   • Histologically or cytologically proven diagnosis of HCC.
   • Typical arterial enhancement and delayed washout on multiphasic CT or MRI.
2. Age ≥18 years at the time of signing informed consent document.
3. ECOG performance status 0-2.
4. Child-Pugh score 5-9 liver function within 28 days of study registration.
5. Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test.
6. Documented virology status of hepatitis C virus (HCV), as confirmed by screening HCV serology test.
7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Presence of distant metastases that cannot be encompassed by radiotherapy
2. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
3. Inability to treat all sites of disease by radiotherapy
4. Known HIV infection.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Radiotherapy; Definitive photon or proton radiotherapy	Radiation: Photon or proton radiotherapy; 39.6-72.6 Gy (or Cobalt Gray Equivalent, CGE) in 22 fractions for tumors ≤1 cm from hepatic hilum, bowel, and heart.; 30-66 Gy (or CGE) in 10 fractions for tumors >1 cm from hepatic hilum, bowel, and heart.; 27.5-60 Gy (or CGE) in 5 fractions using stereotactic body radiation therapy (SBRT) techniques

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	Adverse events will be graded using CTCAE v5	12 months
Local control (LC)	LC is defined as the time from signing the informed consent to the first occurrence of disease progression in the irradiated field according to RECIST1.1.	12 months
Time to progression (TTP)	TTP is defined as the time from signing the informed consent to the first occurrence of disease progression according to RECIST1.1.	12 months
Overall Response Rate (ORR)	ORR is defined as a complete or partial response according to RECIST1.1.	12 months
Overall survival (OS)	OS is defined as the time from signing the informed consent to death from any cause.	12 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2024
• Primary Completion (Estimated): March 17, 2029
• Study Completion (Estimated): March 17, 2032

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 11, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: HCC; Proton Radiotherapy; Photon Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 202400364B0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sharing individual participant data (IPD) with other researchers requires IRB review and approval. Presently, we do not have a plan to provide IPD to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No