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NCT Number: NCT06885879

Impact of Radiotherapy on ctDNA in Patients With Hepatocellular Carcinoma

Radiotherapy is increasingly being used in the management of hepatocellular carcinoma (HCC) as a standalone treatment, or in combination with systemic therapy. Stereotactic Body Radiation Therapy (SBRT) causes cell death directly (via double-stranded breaks) and indirectly (via vascular bed damage or promotion of antitumour immunity). Unfortunately, the effect of cell death is not immediate and takes time. As a result, the typical arterial phase hyperenhancement on imaging may persist up to 12 months after radiotherapy, and it is not necessarily suggestive of presence of viable tumours. Therefore, there is no consensus on ideal timing of response assessment following radiotherapy to HCC. Therefore, a blood-based biomarker which can be done frequently and monitored dynamically, could be preferred for response assessment after radiotherapy. Circulating tumour DNA (ctDNA) is an emerging and promising biomarker in cancer management, which has been shown useful in cancer screening, guiding treatment, and informing prognosis. Currently, most of the clinical applications of ctDNA revolve around either the presence of ctDNA, or the genomic changes associated with these molecules. Biological properties of ctDNA such as fragment length, jaggedness of fragments, or epigenetic changes may provide additional information related to the tumour characteristics and its sensitivity to anti-cancer treatments. These biological properties of ctDNA are relatively unexplored in the context of radiotherapy. It is unknown whether these properties can be utilized for monitoring treatment response. We therefore propose to study the biological properties of ctDNA in relation to HCC patients undergoing radiotherapy.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Clinical Oncology, Prince of Wales Hospital

Hong Kong

Location status: Recruiting

Location contact

Landon L CHAN

CONTACT

[email protected]

MSc, MBChB

Landon L CHAN, MSc, MBChB

PRINCIPAL_INVESTIGATOR

Natalie, KWONG

CONTACT

[email protected]

+852 3505 1040

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged ≥ 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance 0 to 1
  • Confirmed diagnosis of Hepatocellular carcinoma (HCC)
  • Tumour size ≥ 3cm
  • Patients planning on undergoing Stereotactic Body Radiation Therapy (SBRT) for HCC
  • Prior radiofrequency ablation at a different site, or prior surgery are eligible
  • Child-Pugh A liver function
  • Life expectancy longer than 12 weeks
  • At least one measurable treatment lesion according to RECIST 1.1
  • Written informed consent must be obtained prior to any study related procedures
  • Adequate haematological function (Hemoglobin ≥ 8.5g/dL; Platelet Count ≥ 75x109/L; Antenatal Care ≥ 1.5x109/L; international normalised ratio ≤ 1.5)
  • Adequate hepatic function (albumin ≥ 28g/l; Bilirubin ≤ 1.5xULN; Alanine transaminase < 5 times upper limit normal)
  • Adequate renal function (serum creatinine ≤ 1.5 times the upper limit of normal range; Sodium ≥ 130mmol/L; Potassium ≥ 3.0mmol/L)
  • Able to read, understand and provide written consent

Exclusion criteria

  • Histology shows sarcomatoid HCC, fibrolamellar HCC, mixed cholangiocarcinoma-hepatocellular carcinoma
  • Presence of other malignancy than HCC within 5 years from diagnosis of HCC
  • Prior Transarterial chemoembolization (TACE) within 3 months
  • Previous radiotherapy to the abdomen
  • Previous yttrium-90 chemoembolization
  • Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
  • Pregnant or lactating females at any time during the study
  • Active autoimmune disease requiring systemic therapy in the past 2 years
  • Diagnosis of immunodeficiency (including Human Immunodeficiency Viruses)
  • Patients with coagulopathy or on anticoagulant will be excluded from liver biopsy

Treatment and study plan

Temporal change of fragmentomics of Circulating tumour DNA undergoing Stereotactic Body Radiation Therapy investigation

Radiation

Patients will have blood taking for Circulating tumour DNA (ctDNA) (20cc each) at Week 0 (before radiotherapy), Week 1 (during radiotherapy), Week 2 (after radiotherapy), Week 12 and Week 24.

Radiological assessment will be performed before radiotherapy, Week 12 (approximately 3 months post treatment) and Week 24-26 (approximately 6 months post treatment).

Primary outcomes

  1. To characterize the temporal changes of the biological properties of Circulating tumour DNA, including its relative percentage, fragment size, and end-motif fragment pattern for patients undergoing radiotherapy to Hepatocellular carcinoma.

    Time frame: 2 years

Secondary outcomes

  1. To correlate the change in biological properties with response (by RECIST 1.1), survival (e.g. progression-free survival), and toxicities

    Time frame: 2 years

Study contacts

Contact information is provided by the study sponsor or research team.

Landon L CHAN, MSc, MBChB

CONTACT

[email protected]

+852 3505 1042

Natalie KWONG

CONTACT

[email protected]

+852 3505 1040

Sponsors and collaborators

Lead sponsor

Chinese University of Hong Kong

Other

Registry information

Official study title

Impact of Radiotherapy on the Dynamic Changes of Circulating Cell-free DNA in Patients With Hepatocellular Carcinoma

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Mar 20, 2025
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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