Combination of SBRT and Immunotherapy in Small Hepatocellular Carcinoma (HSBRT2402) (HSBRT2402)

November 14, 2024 updated by: Mian XI, Sun Yat-sen University

Stereotactic Body Radiotherapy with or Without Adjuvant Immunotherapy for Small Hepatocellular Carcinoma: an Open-label, Randomized, Phase II Trial

For inoperable small hepatocellular carcinoma (HCC), stereotactic body radiotherapy (SBRT) is an effective and safe local treatment. Despite satisfactory local control rate, the incidence of recurrence out the field remains substantial, with 2-year PFS of 31.9% to 60.9%. Therefore, a more effective treatment mode is urgently needed. Immune checkpoint inhibitors targeting PD-1/PD-L1 have shown substantial clinical benefits in advanced HCC as well as resected high-risk HCC. Recently, the combination of immunotherapy with SBRT has shown promising activity in HCC, but its utility in small HCC is unclear. The aim of this study was to investigate the efficacy and safety of SBRT followed by sintilimab (an anti-PD-1 antibody) in patients with recurrent or residual small HCC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A total of 140 patients with recurrent or residual small HCC will be stratified according to tumor diameter (≤3 vs. >3 cm) and tumor type (recurrent vs. residual) and randomly assigned (1:1) to receive stereotactic body radiotherapy (SBRT) with or without adjuvant sintilimab for 6 cycles (200 mg, once every 3 weeks, with the first dose within 1 week after the completion of SBRT).

Study Type

Interventional

Enrollment (Estimated)

140

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
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Contact:
          • Mian Xi, MD
        • Contact:
          • Qi Zeng, MD
        • Contact:
          • Yi Lu, 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 recurrent or residual HCC lesions without vascular invasion or extrahepatic metastasis confirmed by CT or MRI, the sum of the maximum diameter of lesions ≤5 cm, total number of lesions were ≤2, and at least one of which is measurable according to the RECIST 1.1 Criteria;
  3. Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;
  4. Age at diagnosis 18 to 75 years;
  5. Eastern Cooperative Oncology Group performance status ≤ 2
  6. Child-Pugh class A liver function;
  7. Normal liver volume greater than 700 ml;
  8. Estimated life expectancy ≥24 weeks;
  9. 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;
  10. Ability to understand the study and sign informed consent.

Exclusion Criteria:

  1. Patients who have previously been treated with immune checkpoint inhibitors;
  2. Patients with extrahepatic metastasis disease;
  3. A history of abdominal radiotherapy;
  4. Known or suspected allergy or hypersensitivity to monoclonal antibodies;
  5. Patients who have a preexisting or coexisting bleeding disorder;
  6. Female patients who are pregnant or lactating;
  7. Inability to provide informed consent due to psychological, familial, social and other factors;
  8. A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
  9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
  10. Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
  11. 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;
  12. A history of interstitial lung disease or non-infectious pneumonia;
  13. 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;
  14. 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);
  15. 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week. Then patients in the study group (arm A) will receive sintilimab as adjuvant therapy for up to 6 cycles after the completion of radiotherapy.
Radiation: Stereotactic body radiotherapy
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week.
Other Names:
  • SBRT
Drug: Sintilimab
Patients received sintilimab 200 mg every 3 weeks for up to 6 cycles, with the first dose within 1 week after the completion of SBRT.
Other Names:
  • IBI308
Active Comparator: Arm B
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week. Then patients in the control group (arm B) will be followed up regularly.
Radiation: Stereotactic body radiotherapy
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week.
Other Names:
  • SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) rate
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 24 months
Two-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 24 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
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
Local 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 for the target lesion according to RECIST criteria.
From date of enrollment to the date of last follow-up, 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
Correlation between ctDNA and overall survival
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months
The correlation between dynamic change of ctDNA (before and after treatment) and survival outcomes.
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

Sun Yat-sen University

Collaborators

Fifth Affiliated Hospital, Sun Yat-Sen University
Ningbo Medical Center Lihuili Eastern Hospital

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)

April 5, 2024

Primary Completion (Estimated)

April 30, 2028

Study Completion (Estimated)

April 30, 2030

Study Registration Dates

First Submitted

March 10, 2024

First Submitted That Met QC Criteria

March 10, 2024

First Posted (Actual)

March 15, 2024

Study Record Updates

Last Update Posted (Estimated)

November 18, 2024

Last Update Submitted That Met QC Criteria

November 14, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SL-B2024-061

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to make individual participant data (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

product manufactured in and exported from the U.S.

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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