Hepatocellular CarcinomaPhase 2HSBRT2402NCT06313190
Combination of SBRT and Immunotherapy in Small Hepatocellular Carcinoma (HSBRT2402)
A Phase 2 study testing Stereotactic body radiotherapy and Sintilimab in people with Hepatocellular Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
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%. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Stereotactic body radiotherapy and Sintilimab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteChina
- Study dates
- 5 Apr 2024to 30 Apr 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
- 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;
- Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;
- Age at diagnosis 18 to 75 years;
- Eastern Cooperative Oncology Group performance status ≤ 2
- Child-Pugh class A liver function;
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- Normal liver volume greater than 700 ml;
- Estimated life expectancy ≥24 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.
Who cannot join
- Patients who have previously been treated with immune checkpoint inhibitors;
- Patients with extrahepatic metastasis disease;
- 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;
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- 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);
- Any unstable situation that may endanger the safety and compliance of patients.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Mian Xi, MD, +862087343385, ximian@sysucc.org.cn
Mian Xi, MD
About this study
Official title: 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.
Read the 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).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Stereotactic body radiotherapy, Sintilimab
- Keywords
- Hepatocellular carcinoma, Immunotherapy, Stereotactic body radiotherapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic body radiotherapyRadiation
Also called SBRT
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week.
SintilimabDrug
Also called IBI308
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | 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. Receives: Radiation: Stereotactic body radiotherapy; Drug: Sintilimab |
| Arm B | Active comparator | 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. Receives: Radiation: Stereotactic body radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) rate
Two-year follow-up from the date of enrollment to the date of disease progression or last follow-up
Measured: 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 outcomes (3)
Overall survival
Three-year follow-up from the enrollment to the date of death from any cause or date of lost follow-up
Measured: 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)
The proportion of patients with complete response, partial response, or stable disease for the target lesion according to RECIST criteria.
Measured: From date of enrollment to the date of last follow-up, assessed up to 36 months
Treatment-related adverse events
Incidence of treatment-related adverse events as assessed by CTCAE v4.0.
Measured: From date of enrollment to the date of last follow-up, assessed up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2024
- Study start5 Apr 2024
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Fifth Affiliated Hospital, Sun Yat-Sen University, Ningbo Medical Center Lihuili Hospital
- Responsible party
- Principal investigator, Mian XI, Sun Yat-sen University
- Investigators
- Mian Xi, MD, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06313190
- Sponsor's protocol ID
- SL-B2024-061
- Acronym
- HSBRT2402
- Status last verified
- Nov 2024
- First submitted
- 10 Mar 2024
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to make individual participant data (IPD) available to other researchers.
Publications
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.
PubMed 29366520Chiang 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.
PubMed 36529152Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Qin YY, Shi J, Guo WX, Lu CD, Zheng YX, Zhou FG, Yan ML, Zhou HK, Liang C, Zhang F, Wei WJ, Lau WY, Li JJ, Liu YF, Cheng SQ. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat Med. 2024 Mar;30(3):708-715. doi: 10.1038/s41591-023-02786-7. Epub 2024 Jan 19.
PubMed 38242982Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15.
PubMed 34143971
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic Body Radiotherapy With or Without Adjuvant Immunotherapy for Small Hepatocellular Carcinoma: An Open-label, Randomized, Phase II Trial
- ClinicalTrials.gov ID
- NCT06313190
- Acronym / sponsor ID
- HSBRT2402 / SL-B2024-061
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular carcinoma, Immunotherapy, Stereotactic body radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Fifth Affiliated Hospital, Sun Yat-Sen University, Ningbo Medical Center Lihuili Hospital
- Study start
- 5 Apr 2024 (actual)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 30 Apr 2030 (estimated)
- First posted
- 15 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Radiation: Stereotactic body radiotherapy, Drug: SintilimabPatients 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. |
| Arm B | Active comparator | Radiation: Stereotactic body radiotherapyPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
- 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;
- Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;
- Age at diagnosis 18 to 75 years;
- Eastern Cooperative Oncology Group performance status ≤ 2
Key exclusion criteria (15 listed)
- Patients who have previously been treated with immune checkpoint inhibitors;
- Patients with extrahepatic metastasis disease;
- A history of abdominal radiotherapy;
- Known or suspected allergy or hypersensitivity to monoclonal antibodies;
- Patients who have a preexisting or coexisting bleeding disorder;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic body radiotherapyAlso: SBRTPatients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week. | Radiation | Arm A, Arm B |
| SintilimabAlso: IBI308Patients received sintilimab 200 mg every 3 weeks for up to 6 cycles, with the first dose within 1 week after the completion of SBRT. | Drug | Arm A |
Primary outcome
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
3 secondary outcomes
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
Local control rate (DCR)
Time frame: From date of enrollment to the date of last follow-up, assessed up to 36 months
Treatment-related adverse events
Time frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Results publication: PubMed 29366520Kim 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.
- Results publication: PubMed 36529152Chiang 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.
- Results publication: PubMed 38242982Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Qin YY, Shi J, Guo WX, Lu CD, Zheng YX, Zhou FG, Yan ML, Zhou HK, Liang C, Zhang F, Wei WJ, Lau WY, Li JJ, Liu YF, Cheng SQ. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat Med. 2024 Mar;30(3):708-715. doi: 10.1038/s41591-023-02786-7. Epub 2024 Jan 19.
- Results publication: PubMed 34143971Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15.
- Individual participant dataSharing planned: No. No plan to make individual participant data (IPD) available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mian Xi, MD principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic body radiotherapy and Sintilimab in people with Hepatocellular Carcinoma, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mian Xi, MD (+862087343385, ximian@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06313190, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.