Combination of SBRT, PD-L1 Inhibitor, and Lenvatinib in Hepatocellular Carcinoma (HSBRT2401)

NCT06261125 | Recruiting Phase 2 DMC

• 1 other identifier: SL-B2023-718
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Abdominal lymph node metastasis (LNM) is one of the major modes of extrahepatic metastasis in hepatocellular carcinoma (HCC). Immunotherapy targeting the PD-1/PD-L1 checkpoints combined with targeted therapy is the standard treatment for HCC with abdominal LNM, but the outcome remains very poor, with an objective response rate of 5% to 30%. Previous studies have demonstrated that stereotactic body radiotherapy (SBRT) is an effective local treatment for HCC with abdominal LNM, with a high response rate of 60% to 80%. However, intrahepatic dissemination and distant metastasis remains the major recurrence pattern after SBRT in these patients, suggesting radiotherapy should be combined with systematic treatment. Recently, the combination of immunotherapy with SBRT has shown promising activity in HCC. The aim of this study was to investigate the efficacy and safety of SBRT followed by adebrelimab (an anti-PD-L1 antibody) and lenvatinib in HCC patients with portal abdominal LNM.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Radiotherapy; Immunotherapy; Targeted therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Three-year follow-up from the date of enrollment to the date of disease progression or last follow-up

  From date of enrollment until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 36 months.

Secondary Outcomes (5)

• Overall survival (OS)

  From date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 36 months.

• Overall response rate (ORR)

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Disease control rate (DCR)

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Duration of response (DOR)

  From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.

• Treatment-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Other Outcomes (1)

• Correlation between serum cytokines and overall survival and immune-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Study Arms (2)

Arm A

EXPERIMENTAL

This arm includes the patients who previously had not received PD-1/PD-L1 antibody. Patients assigned to this arm will receive SBRT followed by adebrelimab and lenvatinib. The prescribed dose of SBRT is 33-48 Gy in 6 fractions over 2 weeks. Then all patients will receive lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight \<60 kg) orally once daily in combination with adebrelimab 1200 mg every 3 weeks for up to 35 cycles. The first course of adebrelimab will be given within 1 week after completion of SBRT.

Radiation: Stereotactic body radiotherapy; Drug: Adebrelimab; Drug: Lenvatinib

Arm B

EXPERIMENTAL

This arm includes the patients who had progressed after receiving PD-1/PD-L1 antibody. Patients assigned to this arm will receive SBRT followed by adebrelimab and lenvatinib. The prescribed dose of SBRT is 33-48 Gy in 6 fractions over 2 weeks. Then all patients will receive lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight \<60 kg) orally once daily in combination with adebrelimab 1200 mg every 3 weeks for up to 35 cycles. The first course of adebrelimab will be given within 1 week after completion of SBRT.

Radiation: Stereotactic body radiotherapy; Drug: Adebrelimab; Drug: Lenvatinib

Interventions

Stereotactic body radiotherapy RADIATION

Patients in both cohorts will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 33-48 Gy in 6 fractions over 2 weeks.

Also known as: SBRT

Arm A; Arm B

Adebrelimab DRUG

All patients will reveive adebrelimab 1200 mg every 3 weeks for up to 35 cycles after the completion of SBRT.

Also known as: SHR-1316

Arm A; Arm B

Lenvatinib DRUG

All patients will receive lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight \<60 kg) orally once daily after the completion of SBRT.

Also known as: Lenvima

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
• 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;
• Previous local treatment for intrahepatic lesion and systemic anti-tumor therapy are allowed; no matter whether the disease progressed or not;
• 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;
• 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.
• Age at diagnosis 18 to 75 years;
• Eastern Cooperative Oncology Group performance status ≤ 2
• Child-Pugh class A liver function;
• Normal liver volume greater than 700 ml;
• Estimated life expectancy ≥12 weeks;
• 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;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Diffuse hepatocellular carcinoma;
• Patients who have previously been treated with lenvatinib or PD-1/PD-L1 antibody but could not be tolerated;
• Patients with other extrahepatic metastasis disease except abdominal LNM;
• A history of abdominal radiotherapy;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies;
• Patients who have a preexisting or coexisting bleeding disorder;
• Female patients who are pregnant or lactating;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
• 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;
• A history of interstitial lung disease or non-infectious pneumonia;
• 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;
• 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);

Sponsors & Collaborators

• Mian XI: lead

Study Sites (1)

Mian Xi

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

• Wang Y, Li Q, Zhang L, Liu S, Zhu J, Yang Y, Liu M, Zhang Y, Xi M. Efficacy and Dose-Response Relationship of Stereotactic Body Radiotherapy for Abdominal Lymph Node Metastases from Hepatocellular Carcinoma. Oncologist. 2023 Jun 2;28(6):e369-e378. doi: 10.1093/oncolo/oyad083.

  PMID: 37011232 RESULT

• Kim HJ, Park S, Kim KJ, Seong J. Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy. Radiother Oncol. 2018 Oct;129(1):130-135. doi: 10.1016/j.radonc.2017.11.027. Epub 2018 Jan 30.

  PMID: 29366520 RESULT

• Chiang CL, Chiu KWH, Chan KSK, Lee FAS, Li JCB, Wan CWS, Dai WC, Lam TC, Chen W, Wong NSM, Cheung ALY, Lee VWY, Lau VWH, El Helali A, Man K, Kong FMS, Lo CM, Chan AC. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):169-178. doi: 10.1016/S2468-1253(22)00339-9. Epub 2022 Dec 15.

  PMID: 36529152 RESULT

• Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.

  PMID: 32716739 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery; lenvatinib

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mian Xi, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mian Xi, MD

CONTACT

+862087343385; ximian@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 15, 2024
• Study Start: March 10, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)