Hepatocellular CarcinomaPhase 2/3ISBRT01NCT04167293
Combination of Sintilimab and Stereotactic Body Radiotherapy in Hepatocellular Carcinoma (ISBRT01)
A Phase 2/3 study testing stereotactic body radiotherapy and Sintilimab in people with Hepatocellular Carcinoma, run by Mian XI at 1 site in China.
Trial summary
Although sorafenib is the standard treatment for hepatocellular carcinoma with portal vein invasion, the outcome of these patients remains very poor, with a median survival time of 5.5 to 7.2 months. 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
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteChina
- Study dates
- 16 Nov 2019to 31 Oct 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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;
- No previous treatment for hepatocellular carcinoma, and received arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) as initial treatment and achieved technical success;
- Absence of extrahepatic metastasis disease;
- Portal vein invasion (at least the first- or second-branch portal vein) confirmed by 2 imaging techniques;
- Less than 3 active intrahepatic lesions with a total diameter of less than 15 cm were required, at least one of which is measurable according to the mRECIST Criteria;
- Age at diagnosis 18 to 75 years;
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- 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.
Who cannot join
- Patients who have been treated previously with systemic anti-tumor therapy (including chemotherapy, molecule-targeted therapy, immunotherapy, etc.);
- Patients with extrahepatic metastasis disease at diagnosis;
- The total diameter of the active intrahepatic lesions was more than 15 cm;
- A history of abdominal radiotherapy;
- Known or suspected allergy or hypersensitivity to monoclonal antibodies;
- Patients who have a preexisting or coexisting bleeding disorder;
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- 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);
- Any unstable situation that may endanger the safety and compliance of patients.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Mian Xi, MD, 862087343385, ximian@sysucc.org.cn
About this study
Official title: Effect of Stereotactic Body Radiotherapy Followed by Sintilimab Versus Stereotactic Body Radiotherapy Alone for Hepatocellular Carcinoma With Portal Vein Invasion After Arterially Directed Therapy: A Randomized Clinical Trial
Although sorafenib is the standard treatment for hepatocellular carcinoma with portal vein invasion, the outcome of these patients remains very poor, with a median survival time of 5.5 to 7.2 months. It has been demonstrated that first-line treatment with transarterial chemoembolization plus radiotherapy could provide more favorable survival than sorafenib alone. However, intrahepatic dissemination and distant metastasis remains the major recurrence pattern after treatment in these patients; therefore, searching for new strategies to improve efficacy is necessary. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced HCC. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The aim of this randomized study was to investigate the efficacy and safety of stereotactic body radiotherapy followed by sintilimab (an anti-PD-1 antibody) compared with stereotactic body radiotherapy alone for hepatocellular carcinoma with portal vein invasion after arterially directed therapy.
Read the detailed description
A total of 116 HCC patients with portal vein invasion after arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) will be randomized to two treatment arms using a 1:1 ratio: SBRT + PD-1 arm or SBRT alone arm. Patients in both arms will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. In the SBRT + PD-1 arm, sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- stereotactic body radiotherapy, Sintilimab
- Keywords
- Hepatocellular carcinoma, immunotherapy, PD-1, 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 will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks.
SintilimabDrug
Also called IBI308
Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT.
| Study group | Role | What they receive |
|---|---|---|
| SBRT + PD-1 Arm | Experimental | Patients assigned to this arm will receive SBRT followed by sintilimab. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. In the SBRT + PD-1 arm, sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT. Receives: Radiation: stereotactic body radiotherapy; Drug: Sintilimab |
| SBRT Arm | Other | Patients assigned to this arm will receive SBRT alone. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. Receives: Radiation: stereotactic body radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-week progression-free survival (PFS) rate
The proportion of patients with progression disease according to mRECIST at 24 weeks from randomization.
Measured: 24 weeks after radiotherapy
Secondary outcomes (6)
Progression-free survival (PFS)
From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
Measured: 2 years from randomization
Overall survival (OS)
From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months.
Measured: 2 years from randomization
24-week overall response rate (ORR)
The proportion of patients with complete response or partial response according to mRECIST at 24 weeks from randomization.
Measured: 24 weeks after radiotherapy
24-week disease control rate (DCR)
The proportion of patients with complete response, partial response or stable disease according to mRECIST at 24 weeks from randomization.
Measured: 24 weeks after radiotherapy
Duration of response (DOR)
From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months.
Measured: 2 years from randomization
Adverse Events
Treatment-related adverse events are graded according to the Common Toxicity Criteria, version 4.0, and were registered from the date of informed consent until discontinuation of trial treatment.
Measured: 2 years from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start16 Nov 2019
- Primary completion30 Nov 2021 (estimated)
- Study completion31 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mian XI
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mian XI, Sun Yat-sen University
- Investigators
- Mian Xi, MD, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167293
- Sponsor's protocol ID
- B2019-108-01
- Acronym
- ISBRT01
- Status last verified
- Mar 2021
- First submitted
- 15 Nov 2019
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shi Y, Su H, Song Y, Jiang W, Sun X, Qian W, Zhang W, Gao Y, Jin Z, Zhou J, Jin C, Zou L, Qiu L, Li W, Yang J, Hou M, Zeng S, Zhang Q, Hu J, Zhou H, Xiong Y, Liu P. Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2019 Jan;6(1):e12-e19. doi: 10.1016/S2352-3026(18)30192-3.
PubMed 30612710Shen L, Xi M, Zhao L, Zhang X, Wang X, Huang Z, Chen Q, Zhang T, Shen J, Liu M, Huang J. Combination Therapy after TACE for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: Stereotactic Body Radiotherapy versus Sorafenib. Cancers (Basel). 2018 Dec 14;10(12):516. doi: 10.3390/cancers10120516.
PubMed 30558224Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):661-669. doi: 10.1001/jamaoncol.2017.5847.
PubMed 29543938
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Stereotactic Body Radiotherapy Followed by Sintilimab Versus Stereotactic Body Radiotherapy Alone for Hepatocellular Carcinoma With Portal Vein Invasion After Arterially Directed Therapy: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04167293
- Acronym / sponsor ID
- ISBRT01 / B2019-108-01
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular carcinoma, immunotherapy, PD-1, stereotactic body radiotherapy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Mian XIUniversity, hospital or other
- Study start
- 16 Nov 2019 (actual)
- Primary completion
- 30 Nov 2021 (estimated)
- Study completion
- 31 Oct 2022 (estimated)
- First posted
- 18 Nov 2019 (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.
Although sorafenib is the standard treatment for hepatocellular carcinoma with portal vein invasion, the outcome of these patients remains very poor, with a median survival time of 5.5 to 7.2 months. It has been demonstrated that first-line treatment with transarterial chemoembolization plus radiotherapy could provide more favorable survival than sorafenib alone. However, intrahepatic dissemination and distant metastasis remains the major recurrence pattern after treatment in these patients; therefore, searching for new strategies to improve efficacy is necessary. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced HCC. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The aim of this randomized study was to investigate the efficacy and safety of stereotactic body radiotherapy followed by sintilimab (an anti-PD-1 antibody) compared with stereotactic body radiotherapy alone for hepatocellular carcinoma with portal vein invasion after arterially directed therapy.
Detailed description
A total of 116 HCC patients with portal vein invasion after arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) will be randomized to two treatment arms using a 1:1 ratio: SBRT + PD-1 arm or SBRT alone arm. Patients in both arms will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. In the SBRT + PD-1 arm, sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after 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 |
|---|---|---|
| SBRT + PD-1 Arm | Experimental | Radiation: stereotactic body radiotherapy, Drug: SintilimabPatients assigned to this arm will receive SBRT followed by sintilimab. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. In the SBRT + PD-1 arm, sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT. |
| SBRT Arm | Other | Radiation: stereotactic body radiotherapyPatients assigned to this arm will receive SBRT alone. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
- No previous treatment for hepatocellular carcinoma, and received arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) as initial treatment and achieved technical success;
- Absence of extrahepatic metastasis disease;
- Portal vein invasion (at least the first- or second-branch portal vein) confirmed by 2 imaging techniques;
- Less than 3 active intrahepatic lesions with a total diameter of less than 15 cm were required, at least one of which is measurable according to the mRECIST Criteria;
Key exclusion criteria (16 listed)
- Patients who have been treated previously with systemic anti-tumor therapy (including chemotherapy, molecule-targeted therapy, immunotherapy, etc.);
- Patients with extrahepatic metastasis disease at diagnosis;
- The total diameter of the active intrahepatic lesions was more than 15 cm;
- A history of abdominal radiotherapy;
- Known or suspected allergy or hypersensitivity to monoclonal antibodies;
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 will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. | Radiation | SBRT + PD-1 Arm, SBRT Arm |
| SintilimabAlso: IBI308Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT. | Drug | SBRT + PD-1 Arm |
Primary outcome
24-week progression-free survival (PFS) rate
Time frame: 24 weeks after radiotherapy
The proportion of patients with progression disease according to mRECIST at 24 weeks from randomization.
6 secondary outcomes
Progression-free survival (PFS)
Time frame: 2 years from randomization
Overall survival (OS)
Time frame: 2 years from randomization
24-week overall response rate (ORR)
Time frame: 24 weeks after radiotherapy
24-week disease control rate (DCR)
Time frame: 24 weeks after radiotherapy
Duration of response (DOR)
Time frame: 2 years from randomization
Adverse Events
Time frame: 2 years from randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Results publication: PubMed 30612710Shi Y, Su H, Song Y, Jiang W, Sun X, Qian W, Zhang W, Gao Y, Jin Z, Zhou J, Jin C, Zou L, Qiu L, Li W, Yang J, Hou M, Zeng S, Zhang Q, Hu J, Zhou H, Xiong Y, Liu P. Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2019 Jan;6(1):e12-e19. doi: 10.1016/S2352-3026(18)30192-3.
- Results publication: PubMed 30558224Shen L, Xi M, Zhao L, Zhang X, Wang X, Huang Z, Chen Q, Zhang T, Shen J, Liu M, Huang J. Combination Therapy after TACE for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: Stereotactic Body Radiotherapy versus Sorafenib. Cancers (Basel). 2018 Dec 14;10(12):516. doi: 10.3390/cancers10120516.
- Results publication: PubMed 29543938Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):661-669. doi: 10.1001/jamaoncol.2017.5847.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Mian Xi, MD principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing stereotactic body radiotherapy and Sintilimab in people with Hepatocellular Carcinoma, run by Mian XI 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 12 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 23 Mar 2021. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
24-week progression-free survival (PFS) rate (time frame: 24 weeks after radiotherapy). 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 NCT04167293, which also lists 3 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 23 Mar 2021.