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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fifth Affiliated Hospital, Sun Yat-Sen University
Ningbo Medical Center Lihuili Eastern Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 5, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 15, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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