Intensified versus conversion therapy for advanced liver cancer after first-line bevacizumab plus sintilimab fails

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 interventional trial at Sun Yat-sen University Cancer Center compares two second-line strategies for unresectable hepatocellular carcinoma after progression on first-line bevacizumab plus sintilimab: intensified therapy by adding lenvatinib versus conversion therapy using regorafenib combined with a PD-1 inhibitor. Eligible adults (18–75) must have measurable disease, Child-Pugh A/B liver function, ECOG 0–2, and documented progression after at least two cycles of the prior regimen. Participants will receive one of the two combination regimens and be followed with imaging per mRECIST/RECIST v1.1 and routine safety monitoring to compare response, disease control, and adverse events. Findings will provide exploratory comparative data to help guide selection of second-line options and inform larger confirmatory studies.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Diagnosed with hepatocellular carcinoma (HCC) based on histological or clinical diagnostic criteria;
2. Classified as unresectable HCC following multidisciplinary assessment;
3. Presence of at least one tumor lesion measurable according to EASL criteria;
4. Child-Pugh liver function class A/B, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-2;
5. Disease progression confirmed by CT/MRI and evaluated according to modified RECIST (mRECIST)/RECIST v1.1 criteria after ≥2 cycles of first-line therapy with bevacizumab (15 mg/kg intravenous infusion, once every 3 weeks) combined with sintilimab (200 mg intravenous infusion, once every 3 weeks);
6. Received ≥2 cycles of post-progression treatment with bevacizumab plus sintilimab, lenvatinib, or regorafenib combined with PD-1 inhibitors;
7. Age ≥18 and ≤75 years;
8. Capability to comprehend the study protocol and provide written informed consent;
9. Laboratory parameters: hemoglobin(Hb) ≥8.5 g/dL, white blood cell (WBC) count \>2000/mm³, platelet (PLT) count ≥75,000/mm³, absolute neutrophil count (ANC) \>1500/mm³, total bilirubin ≤30 μmol/L, serum albumin ≥30 g/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN), serum creatinine ≤1.5 times ULN, international normalized ratio (INR) ≤1.5, prothrombin time (PT) ≤18 seconds;
10. Availability of complete baseline data, treatment records, and follow-up data (including imaging assessments, laboratory tests, and clinical documentation).

Exclusion Criteria:

1. Life expectancy ≤2 months;
2. Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies;
3. Active concurrent malignancy or severe comorbid conditions;
4. First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently;
5. Pregnancy or lactation;
6. Known hypersensitivity to study drugs;
7. Clinically significant gastrointestinal bleeding within 30 days prior to enrollment;
8. Refusal to comply with study and/or follow-up procedures.

Where it's running

• Sun Yat-sen University Cancer Center
  Guangzhou, Guangdong, China Recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.