Stage IV HCCPhase 2NCT04547452
Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic HCC
A Phase 2 study testing Stereotactic body radiation therapy and Anti-PD-1 antibody drug named Sintilimab in people with Stage IV HCC and Immunotherapy, run by West China Hospital at 1 site in China.
Trial summary
Hepatocellular carcinoma (HCC) is a common malignancy, and more than 70% of newly diagnosed HCC patients already have advanced disease. Sorafenib and lenvatinib are recommended as first-line options for advanced HCC. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Stage IV HCC, Immunotherapy, SBRT
- What is being tested?
- Stereotactic body radiation therapy and Anti-PD-1 antibody drug named Sintilimab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2020to 1 Jul 2023
- Phase
- Phase 2
- 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 70 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;
- Deemed ineligible for curative intent therapy with surgical resection or liver transplantation.
- Estimated life expectancy ≥12 weeks;
- Male or female subjects with age: 18-70 years old
- Failure in first-line systemic treatment with sorafenib or Lenvatinib
- Unwilling to receive or unable to tolerate first-line treatment with sorafenib
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- Have ECOG performance status 0-1
- Have measurable disease based on RECIST 1.1.
- Pretreatment CT chest /abdomen /pelvis within 28 days of protocol enrollment.
- Child-Pugh class A liver function (assessed within 14 days of SBRT)；
- 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 ≥ 8g/dL; d. serum albumin ≥ 3.0g/dL; e. total bilirubin ≤ 2.0×ULN, ALT, AST ≤ 5×ULN; f. serum creatinine ≤ 1.5×ULN
- Must have at least one lesion amenable to SBRT.
- Ability to understand the study and sign informed consent.
Who cannot join
- A history of abdominal radiotherapy;
- 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);
- 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)
- History of organ transplantation or allogeneic bone marrow transplantation，or other acquired or congenital immunodeficiency diseases
- Receipt of live, attenuated vaccine within 30 days prior to the study treatment
- Has a known history of active TB (Bacillus Tuberculosis).
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- Uncontrolled intercurrent illness including, but not limited to digestive tract ulcer, uncontrolled hypertension, fracture, uncured wound, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
- Female patients who are pregnant or lactating
- Untreated central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression
- Active infection requiring systemic therapy
- Presence of clinically meaningful ascites，hydrothorax or hydropericardium and patients requiring non pharmacologic intervention (eg, paracentesis) or escalation in pharmacologic intervention to maintain symptomatic control
- Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
West China Hospital
Chengdu, Sichuan, 610041
Xin Wang, PhD/MD, +86 28 85423609, wangxin213@sina.com
About this study
Official title: Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a common malignancy, and more than 70% of newly diagnosed HCC patients already have advanced disease. Sorafenib and lenvatinib are recommended as first-line options for advanced HCC. The PD-1 monoclonal antibody，such as nivolumab and pembrolizumab, have been approved to treat the patients with advanced HCC by the FDA. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The purpose of this randomized study is to determine whether stereotactic body radiation therapy (SBRT) combined with sintilimab (an anti-PD-1 antibody) will improve the response to the anticancer treatment compared to sintilimab alone in patients with advanced HCC.
About 84 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.
Read the detailed description
A total of 84 HCC patients who are failure from the first line Sorafenib or lenvatinib treatment will be randomized to two treatment arms using a 1:1 ratio: SBRT + PD-1 arm or PD-1 alone arm.
Patients in both arms will receive sintilimab administered intravenously at 200 mg every 3 weeks. 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
- Stage IV HCC, Immunotherapy, SBRT
- Being tested
- Stereotactic body radiation therapy, Anti-PD-1 antibody drug named Sintilimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic body radiation therapyRadiation
Also called SBRT
Sintilimab Combined with SBRT
Anti-PD-1 antibody drug named SintilimabDrug
Sintilimab
| Study group | Role | What they receive |
|---|---|---|
| Sintilimab Combined with SBRT | Experimental | Patients will be randomly placed in either of the two arms. Participants enrolled in this arm treated to a total dose of 35-80Gy in 5-8 fractions with stereotactic radiotherapy to a liver or lung or any metastatic lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist.
Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. Receives: Radiation: Stereotactic body radiation therapy; Drug: Anti-PD-1 antibody drug named Sintilimab |
| Sintilimab | Active comparator | Participants enrolled in this arm treated with sintilimab administered intravenously at 200 mg every 3 weeks for up to 1 year. Receives: Drug: Anti-PD-1 antibody drug named Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-week progression-free survival (PFS) ratev
The proportion of patients with progression disease according to mRECIST at 24 weeks from randomization.
Measured: 24 weeks after radiotherapy
Secondary outcomes (5)
Objective Response Rate (ORR)
Investigator assessed ORR using RECIST v1.1 including the all tumor, the tumor undergoing LDRT and the tumor which do not receive radiotherapy.
Measured: up to 24 months after the enrollment
Overall Survival (OS)
OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause
Measured: up to 24 months after the enrollment
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: up to 24 months after the enrollment
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 posted14 Sep 2020
- Study start1 Jul 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV HCCStudies of the same condition, open and under way.
- More trials run by West China HospitalThe 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
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Xin, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04547452
- Sponsor's protocol ID
- I-SBRT-HCC-001
- Status last verified
- Jul 2020
- First submitted
- 6 Sep 2020
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04547452
- Acronym / sponsor ID
- I-SBRT-HCC-001
- Conditions
- Stage IV HCC, Immunotherapy, SBRT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 14 Sep 2020 (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.
Hepatocellular carcinoma (HCC) is a common malignancy, and more than 70% of newly diagnosed HCC patients already have advanced disease. Sorafenib and lenvatinib are recommended as first-line options for advanced HCC. The PD-1 monoclonal antibody，such as nivolumab and pembrolizumab, have been approved to treat the patients with advanced HCC by the FDA. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The purpose of this randomized study is to determine whether stereotactic body radiation therapy (SBRT) combined with sintilimab (an anti-PD-1 antibody) will improve the response to the anticancer treatment compared to sintilimab alone in patients with advanced HCC.
About 84 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.
Detailed description
A total of 84 HCC patients who are failure from the first line Sorafenib or lenvatinib treatment will be randomized to two treatment arms using a 1:1 ratio: SBRT + PD-1 arm or PD-1 alone arm.
Patients in both arms will receive sintilimab administered intravenously at 200 mg every 3 weeks. 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 |
|---|---|---|
| Sintilimab Combined with SBRT | Experimental | Radiation: Stereotactic body radiation therapy, Drug: Anti-PD-1 antibody drug named SintilimabPatients will be randomly placed in either of the two arms. Participants enrolled in this arm treated to a total dose of 35-80Gy in 5-8 fractions with stereotactic radiotherapy to a liver or lung or any metastatic lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist. Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. |
| Sintilimab | Active comparator | Drug: Anti-PD-1 antibody drug named SintilimabParticipants enrolled in this arm treated with sintilimab administered intravenously at 200 mg every 3 weeks for up to 1 year. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
- Deemed ineligible for curative intent therapy with surgical resection or liver transplantation.
- Estimated life expectancy ≥12 weeks;
- Male or female subjects with age: 18-70 years old
- Failure in first-line systemic treatment with sorafenib or Lenvatinib
Key exclusion criteria (13 listed)
- A history of abdominal radiotherapy;
- 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);
- 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)
- History of organ transplantation or allogeneic bone marrow transplantation，or other acquired or congenital immunodeficiency diseases
- Receipt of live, attenuated vaccine within 30 days prior to the study treatment
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 radiation therapyAlso: SBRTSintilimab Combined with SBRT | Radiation | Sintilimab Combined with SBRT |
| Anti-PD-1 antibody drug named SintilimabSintilimab | Drug | Sintilimab, Sintilimab Combined with SBRT |
Primary outcome
24-week progression-free survival (PFS) ratev
Time frame: 24 weeks after radiotherapy
The proportion of patients with progression disease according to mRECIST at 24 weeks from randomization.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: up to 24 months after the enrollment
Overall Survival (OS)
Time frame: up to 24 months after the enrollment
24-week disease control rate (DCR)
Time frame: 24 weeks after radiotherapy
Duration of response (DOR)
Time frame: up to 24 months after the enrollment
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 14 Sep 2020.
- 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.
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 radiation therapy and Anti-PD-1 antibody drug named Sintilimab in people with Stage IV HCC and Immunotherapy, run by West China Hospital 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 13 inclusion and 13 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 14 Sep 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xin Wang, PhD/MD (+86 28 85423609, wangxin213@sina.com), 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) ratev (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?
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 14 Sep 2020.