Radiotherapy Delays Second-line Drug Therapy for Oligo Progressive Primary Liver Cancer

NCT06261047 | Completed

• 1 other identifier: SDZLEC2023-389-02
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Recent years have seen significant advancements in the treatment landscape of advanced hepatocellular carcinoma (HCC), with the emergence of targeted and immunotherapy strategies reshaping first-line therapy. Sorafenib, a multi-targeted tyrosine kinase inhibitor, initially set the standard, followed by approvals for lenvatinib, regorafenib, cabozantinib, and ramucirumab. Immunotherapy, particularly combinations like atezolizumab with bevacizumab, has shown superior efficacy over sorafenib. Despite these advances, second-line therapies offer limited progression-free survival (mPFS: 2-3 months), necessitating new approaches. Radiotherapy, bolstered by technological advancements, has shown promise. Techniques like stereotactic body radiotherapy (SBRT) combined with PD-1 inhibitors achieve significant response rates and survival benefits. Combining radiotherapy with targeted immunotherapy has also demonstrated improved outcomes. Radiotherapy, especially in oligometastatic HCC, is increasingly favored due to its ability to enhance local control without increasing toxicity. These developments underscore the evolving landscape of HCC treatment towards personalized and multimodal approaches.

Conditions

Hepatocellular Carcinoma; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The time from the initiation of radiotherapy until disease progression or death, whichever occurs first.

  1 year

Secondary Outcomes (4)

• Overall response rate

  1 year

• Overall survial

  1 year

• Disease control rate

  1 year

• Duration of control

  1 year

Interventions

radiotherapy RADIATION

radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Hepatocellular carcinoma, stage IIIB, oligo progress

You may qualify if:

• Obtain written informed consent before implementing any trial-related procedures.
• Male or female, aged 18 years or older, and 75 years or younger.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Histological or cytological confirmation of primary hepatocellular carcinoma (HCC), or diagnosed according to the Clinical Diagnosis and Treatment Guidelines for Primary - Liver Cancer (2019 edition) issued by the National Health Commission of the People's Republic of China.
• Tumor staged as BCLC stage C; patients have ≤5 lesions (≤3 affected organs) with oligometastasis or oligoprogression.
• Liver function assessed by Child-Pugh score ≤7 points.
• Availability of tumor samples for biomarker assessment.
• Stable disease with systemic therapy for ≥3 months and an anticipated survival period of ≥6 months.

You may not qualify if:

• Diagnosis of malignancy other than liver cancer within 3 years before enrollment (excluding curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma).
• Currently participating in interventional clinical research treatment, or received other investigational drugs or investigational device therapy within the past 4 weeks before enrollment.
• Received traditional Chinese medicine or immunomodulatory drugs with anti-tumor indications within 2 weeks before enrollment (including thymosin, interferon, interleukin, except for local use to control pleural effusion).
• Experienced active autoimmune diseases requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressive agents) within 2 years before enrollment. Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Received radiotherapy within 2 weeks before enrollment.
• HIV +
• Active untreated hepatitis B (defined as HBsAg positive with HBV-DNA copy number exceeding the upper limit of normal value in the laboratory of the participating center).
• Pregnant or lactating women.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Jinbo Yue

Jinan, Shandong, 250000, China

Location

Related Publications (6)

• Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):7. doi: 10.1038/s41572-021-00245-6. No abstract available.

  PMID: 33479233 RESULT

• Lee S, Kang TW, Song KD, Lee MW, Rhim H, Lim HK, Kim SY, Sinn DH, Kim JM, Kim K, Ha SY. Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation. Ann Surg. 2021 Mar 1;273(3):564-571. doi: 10.1097/SLA.0000000000003268.

  PMID: 31058694 RESULT

• Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

  PMID: 29433850 RESULT

• Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.

  PMID: 27932229 RESULT

• Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

  PMID: 29875066 RESULT

• Wang H, Zhang X, Zhu K, Jiang S, Liu T, Feng R, Dou X, Xu L, He J, Shi F, Yue J. Efficacy and safety of radiotherapy to delay second-line systemic therapy in patients with oligoprogressive hepatocellular carcinoma: study protocol of a multicentre, single-arm, phase II trial. Ther Adv Med Oncol. 2025 Apr 23;17:17588359251334538. doi: 10.1177/17588359251334538. eCollection 2025.

  PMID: 40297623 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiotherapy

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)

Therapeutics

Study Officials

• jibo yue, dorctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: jinbo Yue

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 15, 2024
• Study Start: March 1, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)