A Study of Standard Of Care Versus Radio Ablation in Early Stage HCC (SOCRATES HCC)

A Randomized Controlled Trial of Standard Of Care Versus Radio Ablation in Early Stage Hepatocellular Carcinoma

This Phase II Prospective, parallel and open-label randomised control trial will investigate whether a radiotherapy technique (called SABR) can treat early stage liver cancer more effectively than current treatments which use heating probes directly inserted into the tumour or chemotherapy or radioactive particles injected into the blood supply of the tumour. Investigators hypothesize SABR will result in higher rates of freedom from local progression (FFLP) at 2 years compared to percutaneous thermal ablation ± TACE or transarterial therapies (TACE/TARE).The study will also look at other important outcomes such as progression free survival, overall survival, side effects, quality of life and people's experiences of their treatment.

Study Overview

• Status: Recruiting
• Conditions: Early Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Stereotactic Ablative Body Radiotherapy (SABR); Radiation: Therapies

Detailed Description

The SOCRATES randomised controlled trial will assess the efficacy, toxicity, HRQoL profile and cost effectiveness of SABR compared to the current SOC treatment in patients with first diagnosis of unresectable, single nodule HCC. Participants will be placed into one of two groups based on the size of their tumour and whether thermal ablation is an appropriate treatment for them. The study will include about 218 participants in total. Participants will be randomly assigned to receive either SABR or the current standard of care. Standard care may include thermal ablation, transarterial chemoembolisation (TACE), or transarterial radioembolisation (TARE).

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Yan, MD MPH FRCPC DABR; Phone Number: (416) 946-2320; Email: Michael.Yan@uhn.ca

Study Locations

• Australia
  • Waratah, Australia
    • Recruiting
    • Trans Tasman Radiation Oncology Group
    • Contact: Alan Wigg; Email: Alan.wigg@sa.gov.au
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network - Princess Margaret Cancer Centre
      • Contact: Michael Yan, MD MPH FRCPC DABR; Email: Michael.Yan@uhn.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1) Histological or radiological diagnosis of single, new HCC with largest diameter =8 cm (BCLC stage 0 or A).

• a) If prior history of HCC, the prior HCC must have been:
• Early stage, solitary HCC, =5 cm in size and,
• Have arisen within a different liver segment to the current HCC and,
• Treated with curative intent therapy >2 years prior with no evidence of active disease at the site.
• 2) As per local multidisciplinary HCC meeting consensus patient is suitable for percutaneous thermal ablation and/or transarterial therapies and not suitable for or declined liver resection and not planned for liver transplantation.
• 3) Child-Pugh score =B7* with no or diuretic-controlled ascites
• 4) ECOG performance status =2
• 5) Platelets =50x109/L, Haemoglobin =80 g/L, Neutrophils =1.0x109/L, INR <1.8 (except if on therapeutic anticoagulation)
• 6) 18 years of age or older and able to provide written consent

Exclusion Criteria:

• 1) Presence of multifocal HCC, macrovascular invasion or extrahepatic disease
• 2) Prior treatment for any HCC within last 2 years.
• 3) Clinically evident ascites or hepatic encephalopathy
• 4) Prior abdominal radiation therapy that would preclude the delivery of protocol defined SABR to the tumour.
• 5) Untreated Hepatitis B or C
• 6) Known additional invasive malignancy (excluding non-melanoma skin cancer) that is progressing or required treatment within the last 2 years.
• 7) Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation Therapy	Radiation: Stereotactic Ablative Body Radiotherapy (SABR); SABR will be delivered in 3 or 5 outpatient treatment sessions (each 20 to 45 minutes in duration) spaced out over 1 to 2 weeks. The exact number of treatment sessions received, and the duration of each session depends on the size and location of the liver cancer.
Other: Standard Of Care Treatment	Radiation: Therapies; Patients will receive standard of care treatment (SOC) as per their institution's local practice that will be administered by a doctor called an Interventional Radiologist. The therapies offered will depend on the size and location of the liver cancer and may include one or a combination of radiofrequency ablation (RFA) / microwave ablation (MWA) and/or transarterial chemoembolization (TACE) / transarterial radioembolisation (TARE).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Freedom from local progression (FFLP)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		2 years
Progression-free survival (PFS)		2 years
Safety and adverse events (CTCAE v5.0)		2 Years
Patient reported outcomes (EORTC QLQ-C30)	The C30 is a 30-item instrument that evaluates HRQOL comprised of five functional scales (physical, cognitive, emotional, social, and role) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, anorexia, constipation, diarrhea, and financial), and a global QoL scale. Responses are scored on a linear scale from 0 to 100. Higher scores on functioning/global health indicate a better, healthier state. Higher scores on symptom scales indicate a higher symptom burden or worse condition.	2 Years
Patient reported outcomes (QLQ-HCC18)	QLQ-HCC18 is a questionnaire where patients report symptoms or problems on a scale of 1 (not much) to 4 (very much). Higher scores on symptom scales indicate a higher symptom burden or worse condition.	2 Years
Cost-effectiveness analysis	Incremental cost per outcome	2 Years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Australasian Gastro-Intestinal Trials Group; Trans Tasman Radiation Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2026
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: TACE; Radiofrequency ablation; RFA; SABR; Transarterial chemoembolisation; TARE; Stereotactic Ablative Body 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; Therapeutics
• Other Study ID Numbers: 25-5862; ACTRN12621001444875 (Other Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR))

Drug and device information, study documents

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