Post-surgery radiotherapy plus sintilimab versus TACE for liver cancer with narrow surgical margins

Adjuvant Radiotherapy Combined With Sintilimab Versus Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma With Narrow Margins and High-Risk Features Following Resection: A Multi-center Phase III Randomized Controlled Trial

This trial will try to see if adding radiotherapy and the immunotherapy drug sintilimab after curative liver cancer surgery prevents recurrence better than TACE in patients with narrow surgical margins and other high-risk features.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 286 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (other)
• Drugs / interventions: chemotherapy, sintilimab
• Locations: 1 site (Beijing)
• Trial ID: NCT07186621 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized phase III trial randomizing patients 1:1 to either adjuvant radiotherapy with concurrent and maintenance sintilimab or to postoperative TACE. The radiotherapy arm delivers 44–50 Gy to the tumor bed and 56–60 Gy to narrow‑margin areas in 22–25 fractions, with sintilimab 200 mg every 3 weeks for 2 concurrent cycles followed by up to 15 maintenance cycles. The TACE arm receives the first embolization within 4 months after surgery, with additional TACE per investigator judgment. The primary endpoint is 2‑year recurrence‑free survival, and secondary endpoints include 2‑year overall survival and treatment safety.

Who should consider this trial

Good fit: Adults 18–80 who had R0 resection with a surgical margin <1 cm within the past 4 months, have at least one high‑risk feature (microvascular invasion, tumor thrombus or satellite nodules; AFP >400 ng/mL; or tumor >5 cm with incomplete capsule), ECOG 0–1, and Child‑Pugh A5–A6 or B7 with acceptable ALT/AST limits are ideal candidates.

Not a fit: Patients with wider surgical margins, residual intrahepatic lesions, uncontrolled liver dysfunction beyond eligibility cutoffs, poor performance status, or who cannot start treatment within the 4‑month postoperative window are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could lower postoperative recurrence and improve survival for patients with narrow‑margin HCC.

How similar studies have performed: While adjuvant radiotherapy and immune checkpoint inhibitors have shown encouraging signals in smaller or nonrandomized HCC studies, using radiotherapy plus sintilimab versus TACE in narrow‑margin patients is relatively novel and not yet proven in phase III trials.

Eligibility criteria

Inclusion Criteria:

1. R0 resection of hepatocellular carcinoma (HCC) with a surgical margin \<1 cm (determined by postoperative pathology, surgical records, and imaging).
2. Within 4 months after curative resection.
3. High-Risk Recurrence Factors (at least one required in addition to narrow margin): (1) Microvascular invasion (MVI) positive, tumor thrombus, or satellite nodules (2) Preoperative AFP \>400 ng/mL (3) Tumor \>5 cm with incomplete capsule
4. ≥18 and ≤80 years old.
5. ECOG score 0-1.
6. Child-Pugh Class: A5, A6, or B7.
7. Postoperative Contrast-enhanced MRI of the liver must be performed to exclude intrahepatic residual lesions.
8. HBV DNA and HCV RNA status do not affect eligibility, but if HBV DNA positive and/or HCV RNA positive: ALT must be \<1.5× upper limit of normal (ULN). Antiviral therapy must be initiated.
9. Liver Function Tests (LFTs): ALT ≤2.5× ULN (if HBV/HCV positive, ALT ≤1.5× ULN). If ALT ≤1.5× ULN, AST ≤6× ULN (excluding AST elevation due to myocardial infarction). If ALT 1.5-2.5× ULN, AST ≤2.5× ULN.
10. No significant ECG abnormalities and no severe cardiac dysfunction.
11. Serum creatinine (CRE) and BUN ≤2.5× ULN.
12. Hb≥80g/L，ANC≥1.0×109 /L，PLT≥40×109 /L.
13. Written informed consent obtained.

Exclusion Criteria:

1. Vp3 or Vp4 portal vein tumor thrombus (PVTT) or Vv2/Vv3 inferior vena cava (IVC) tumor thrombus on preoperative imaging.
2. Previous anti-HCC therapies, including but not limited to: targeted therapy (e.g., tyrosine kinase inhibitors), immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) or systemic chemotherapy
3. Distant metastasis before randomization.
4. Moderate to severe ascites unresponsive to medical management.
5. History of other malignancies, except: carcinoma in situ，early-stage papillary thyroid cancer or basal cell carcinoma of the skin
6. Previous radiotherapy involving the abdomen.
7. Significant cardiac, renal, or other major organ dysfunction.
8. Active Autoimmune Disease or Psychiatric Disorders.
9. HIV Infection.
10. Pregnant or breastfeeding women.
11. Currently enrolled in another interventional clinical trial.

Where this trial is running

Beijing

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences — Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Bo Chen, MD.

Conditions: Hepatocellular Carcinoma, Radiotherapy, Adjuvant, Immune Checkpoint Inhibitor, TACE, Narrow Margin, hepatocellular carcinoma, radiotherapy, narrow margin