SBRT in HCC With Oligoprogression on First-line Immunotherapy

Stereotactic Body Radiotherapy (SBRT) in Advanced Hepatocellular Carcinoma With Oligoprogression on First-line Immunotherapy

HCC is a huge healthcare burden in Hong Kong and is one of the top 5 cancers in terms of incidence and mortality in Hong Kong. Patients with advanced HCC are treated with immunotherapy-based as first-line treatment as a standard of care. At the moment, there is limited evidence to guide subsequent treatments after patients progressed on immunotherapy. Oligoprogression is a term used to describe patients who had limited progression (usually less than 3 sites) on systemic therapy, with the rest of the lesions controlled. Previous studies in non-HCCs have shown that addition of locoregional treatment (e.g. radiotherapy) may prolong the use of systemic therapy, resulting in improved survival, but this has been relatively unexplored for HCC. In this prospective, single-arm study, we aim to evaluate the treatment outcome, efficacy and safety of the addition of radiotherapy to oligoprogressive sites for patients who had limited progression on First-line Immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: HCC
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Landon L CHAN, MBChB, MSc; Phone Number: 3505 1042; Email: landon.chan@cuhk.edu.hk
• Study Contact Backup: Name: Natalie KWONG, RN; Phone Number: 3505 1040; Email: nataliekwong019@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Prince of Wales Hospital
    • Contact: Landon L CHAN, MBChB, MSc; Phone Number: 3505 1042; Email: landon.chan@cuhk.edu.hk
    • Contact: Natalie KWONG, RN; Phone Number: 3505 1040; Email: nataliekwong019@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged ≥ 18 years old
2. ECOG performance 0 to 1
3. Confirmed diagnosis of HCC

4. Oligoprogression on first-line immunotherapy, as defined as ≤ 5 lesions (intra- and extrahepatic lesions all together; vascular tumor thrombus is counted as one lesion)

   • First-line immunotherapy that are allowed in this study include atezolizumab plus bevacizumab, durvalumab plus tremelimumab, durvalumab, nivolumab and ipilimumab, which are approved by the FDA and have been used in Hong Kong.

5. Progressed lesion(s) amenable to SBRT:

   • For intrahepatic progression:

     • Number of intrahepatic progression ≤ 5
     • Total intrahepatic tumours ≤ 10
     • Maximum sum of HCC ≤ 20cm
     • Any one HCC ≤ 20cm
     • Normal liver volume minus intrahepatic GTV > 700cc
     • Mean liver dose ≤ 15Gy
     • No measurable common or main branch biliary duct involvement
     • No direct tumor invasion into the stomach, duodenum, small bowel or large bowel

   • For extrahepatic progression:

     • Maximal tumor size ≤ 7cm
     • Respective dose constraints of organ at risks as listed on the UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy can be met and ASTRO guideline.
6. Prior radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) are eligible
7. Child-Pugh A liver function
8. Life expectancy longer than 12 weeks
9. At least one measurable treatment lesion according to RECIST 1.1
10. Written informed consent must be obtained prior to any study related procedures
11. Adequate haematological function (Hb ≥ 8.5g/dL; Plt ≥ 50x10^9/L; ANC ≥ 1.0x10^9/L; INR ≤ 1.5)
12. Adequate hepatic function (albumin ≥ 28g/L; Bilirubin ≤ 2.5xULN; ALT < 5 times upper limit normal)
13. Adequate renal function (serum creatinine ≤ 1.5 times the upper limit of normal range; Na ≥ 130mmol/L; K ≥ 3.0mmol/L)
14. Able to read, understand and provide written consent

Exclusion Criteria:

1. History of another malignancy except appropriately-treated BCC of skin or CIN of cervix during the last 5 years
2. Previous radiotherapy to the abdomen
3. Previous yttrium-90 chemoembolization
4. Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
5. Pregnant or lactating females at any time during the study
6. Active autoimmune disease requiring systemic therapy in the past 2 years
7. Diagnosis of immunodeficiency (including HIV)
8. Ongoing corticosteroid therapy >10mg prednisone daily

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiotherapy; Suitable patients are consented and enrolled with the following treatment being given.; Continue of immunotherapy till next progression, intolerability, or death as per standard practice.; Radiotherapy will start 4 to 6 weeks after consent; For intrahepatic progression: 27.5-50Gy in 5 fractions over 2 weeks is generally recommended.; For extrahepatic progression: delivery of ablative dose (i.e. BED10≥100Gy) will be attempted.; Lower doses to be delivered (for both intrahepatic and extrahepatic lesions) based on nearby OAR dose constraints are allowed. The final dose and fractionation are at the discretion of the treating oncologist.; Bevacizumab will need to be withhold 4 weeks prior and after radiotherapy. PD-1 or PD-L1 therapy are allowed to be continued as per the latest ESTRO-ESMO consensus guideline.; Dose constraints to organ at risk (OAR) will take reference from RTOG-1112 and UK 2022 consensus on normal tissue dose-volume constraints and ASTRO 2022 guideline.

Radiation: Stereotactic Body Radiation Therapy (SBRT); For intrahepatic progression: 27.5-50Gy in 5 fractions over 2 weeks is generally recommended.; For extrahepatic progression: delivery of ablative dose will be attempted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS) with the addition of SBRT to oligo-progressive sites	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		2 years
Objective response rates (ORR) of the irradiated lesion(s)		2 years
Overall objective response rates (ORR)		2 years
Additional treatment related adverse events (TRAE)		2 years
Pattern of progression	Four types of progression pattern: EHG (extrahepatic growth); IHG (intrahepatic growth); NEH (new extrahepatic lesion); NIH (new intrahepatic growth)	2 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: SBRT in HCC
• Additional Relevant MeSH Terms: Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: HCC078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No