Combining radiotherapy and immunotherapy for liver cancer with lymph node metastasis

Efficacy and Safety of Stereotactic Body Radiotherapy Followed by Adebrelimab and Lenvatinib for Hepatocellular Carcinoma With Abdominal Lymph Node Metastases: A Two-arm, Phase II Trial

This study is testing a new treatment that combines radiation therapy with two medications to see if it helps people with liver cancer that has spread to lymph nodes feel better and have better results than current treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: lenvatinib, adebrelimab, Immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06261125 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness and safety of combining stereotactic body radiotherapy (SBRT) with the PD-L1 inhibitor adebrelimab and the targeted therapy lenvatinib in patients with hepatocellular carcinoma (HCC) that has spread to abdominal lymph nodes. A total of 60 patients will be enrolled and divided into two cohorts based on their previous treatment history with PD-1/PD-L1 antibodies. Participants will receive SBRT followed by lenvatinib and adebrelimab, with the aim of improving response rates compared to existing treatments. The study will assess both the efficacy of this combination therapy and its safety profile.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with histologically confirmed hepatocellular carcinoma and abdominal lymph node metastasis.

Not a fit: Patients with extensive extrahepatic metastasis or those with Child-Pugh class B or C liver function will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with hepatocellular carcinoma and abdominal lymph node metastasis.

How similar studies have performed: Previous studies have shown promising results with similar combinations of radiotherapy and immunotherapy in hepatocellular carcinoma, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
2. Presence of abdominal metastatic lymph nodes confirmed by CT or MRI, the sum of the maximum diameter of lymph nodes ≤10 cm, and at least one of which is measurable according to the RECIST 1.1 Criteria;
3. Previous local treatment for intrahepatic lesion and systemic anti-tumor therapy are allowed; no matter whether the disease progressed or not;
4. Less than 3 active intrahepatic lesions with a total diameter of less than 10 cm; Portal vein invasion is allowed; absence of other extrahepatic metastasis disease except abdominal LNM;
5. Cohort 1: Patients who never received PD-1/PD-L1 antibody therapy; Cohort 2: patients who had tumor progression after previous PD-1/PD-L1 antibody therapy.
6. Age at diagnosis 18 to 75 years;
7. Eastern Cooperative Oncology Group performance status ≤ 2
8. Child-Pugh class A liver function;
9. Normal liver volume greater than 700 ml;
10. Estimated life expectancy ≥12 weeks;
11. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 50×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate \>60 mL/min;
12. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. Diffuse hepatocellular carcinoma;
2. Patients who have previously been treated with lenvatinib or PD-1/PD-L1 antibody but could not be tolerated;
3. Patients with other extrahepatic metastasis disease except abdominal LNM;
4. A history of abdominal radiotherapy;
5. Known or suspected allergy or hypersensitivity to monoclonal antibodies;
6. Patients who have a preexisting or coexisting bleeding disorder;
7. Female patients who are pregnant or lactating;
8. Inability to provide informed consent due to psychological, familial, social and other factors;
9. A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
10. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
11. Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
12. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
13. A history of interstitial lung disease or non-infectious pneumonia;
14. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
15. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay);
16. Any unstable situation that may endanger the safety and compliance of patients.

Where this trial is running

Guangzhou, Guangdong

• Mian Xi — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Mian Xi, MD — Sun Yat-sen University
• Study coordinator: Mian Xi, MD

Conditions Hepatocellular Carcinoma; Hepatocellular carcinoma; Radiotherapy; Immunotherapy; Targeted therapy