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

March 10, 2024 updated by: Mian XI

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A total of 60 HCC patients (2 cohorts) with abdominal LNM will be enrolled to receive SBRT followed by adebrelimab (an anti-PD-L1 antibody) and lenvatinib. Arm A included the patients who previously had not received PD-1/PD-L1 antibody, and Arm B included the patients who had progressed after receiving PD-1/PD-L1 antibody.

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. 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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Mian Xi
        • Contact:
        • Principal Investigator:
          • Mian XI, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
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
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.
Other Names:
  • SBRT
Drug: Adebrelimab
All patients will reveive adebrelimab 1200 mg every 3 weeks for up to 35 cycles after the completion of SBRT.
Other Names:
  • SHR-1316
Drug: Lenvatinib
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.
Other Names:
  • Lenvima
Experimental: Arm B
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
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.
Other Names:
  • SBRT
Drug: Adebrelimab
All patients will reveive adebrelimab 1200 mg every 3 weeks for up to 35 cycles after the completion of SBRT.
Other Names:
  • SHR-1316
Drug: Lenvatinib
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.
Other Names:
  • Lenvima

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-related adverse events
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
Incidence of treatment-related adverse events as assessed by CTCAE v4.0.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Overall survival (OS)
Time Frame: 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.
Three-year follow-up from the enrollment to the date of death from any cause or date of lost follow-up
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)
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
Tumor response was evaluated every 9 weeks after the completion of radiotherapy based on CT or MRI scan.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Disease control rate (DCR)
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The proportion of patients with complete response, partial response, or stable disease according to RECIST criteria.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Duration of response (DOR)
Time Frame: From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.
From the date of first CR/PR to the date of first PD.
From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between serum cytokines and overall survival and immune-related adverse events
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The correlation between dynamic change of serum cytokines (IL-2R, IL-6, IL-13, IL-8, CCL3, CD40, and CD274) during treatment and survival outcomes and immune-related adverse events.
From date of enrollment to the date of last follow-up, assessed up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mian XI

Investigators

  • Principal Investigator: Mian Xi, MD, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

February 8, 2024

First Submitted That Met QC Criteria

February 8, 2024

First Posted (Actual)

February 15, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 10, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SL-B2023-718

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make IPD available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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