RadiotherapyPhase 3NCT04709380
Phase III RCT of Radiotherapy Plus Toripalimab Versus Sorafenib in Advanced Hepatocellular Carcinoma With PVTT
A Phase 3 study testing Radiotherapy plus Toripalimab and Sorafenib in people with Radiotherapy and Toripalimab, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
To explore the efficacy of radiotherapy plus toripalimab Versus standard treatment of sorafenib in advanced hepatocellular carcinoma with Portal Vein/Hepatic vein Tumor Thrombosis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Radiotherapy, Toripalimab, Sorafenib
- What is being tested?
- Radiotherapy plus Toripalimab and Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2021to 5 Feb 2025
- Phase
- Phase 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical or histologic diagnosis of Hepatocellular carcinoma (HCC) according to the 2019 version of liver cancer diagnosis and treatment guideline.
- Aged between 18 and 80 years.
- ECOG 0-1.
- The left volume of liver-GTV which is received less than dose of 5Gy is more than 250ml after the portal vein/hepatic vein tumor thrombosis and its connected primary main lesion is received treatment dose of 40-60Gy/10-20f.
- Patients may have a history of treatments for hepatocellular carcinoma such as TACE, radiofrequency, surgery, chemotherapy, and Chinese herbal medicine, but all patients must have not been received targeted therapy and Immunotherapy, such as anti-PD-1, anti-PD-L1 or anti-PD-L2 drug therapy.
- BCLC Stage C, HCC combined with portal vein or hepatic vein tumor thrombosis. If it is a portal vein tumor thrombosis, it must involve the left or right portal trunk at least. If it is a hepatic vein tumor thrombosis, it must involve the left or middle or right main hepatic veins at least. At the same time, eligible patients have to meet one of the following conditions. (1) There are distant metastases (except for central nervous system and meningeal metastases); (2) Both hepatic lobes are showed multiple lesions which are unable to be fully covered within the target area; (3) portal vein tumor thrombosis involved main portal trunk.
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- The expected lifetime is more than 3 months.
- Child A5, A6, B7.
- Virus conditions: HBV DNA <2000 IU/mL, if ≥ 2000 IU/mL, need to accept antiviral treatment until<2000 IU/mL; patients with a positive HCV antibody must have a negative polymerase chain reaction (PCR) test result of HCV RNA;
- Liver function: ALT is within 2.5 times of the upper limit of normal. AST can be within 6 times of the upper limit of normal if ALT is within 1.5 times of the upper limit of normal and cardiac infarction is excluded. If ALT is 1.5 to 2.5 times the upper limit of normal, AST must be within 1.5 times the upper limit of normal.
- There is no obvious abnormality in the electrocardiography, and no obvious cardiac dysfunction.
- Renal function: CRE and BUN are within 1.5 times the upper limit of normal.
- Blood routine test: Hb≥80g/L, ANC≥1.0×10 9/L, PLT≥40×10 9/L.
- Coagulation function: no bleeding tendency.
- Willingness to voluntarily participate in the clinical trial and sign informed consent..
Who cannot join
- Those who are participating in other clinical trials.
- Had prior abdominal irradiation, or had prior liver transplantation.
- Patients with chronic, serious diseases such as cardiac, pulmonary, and renal disease.
- Suspected or true alcohol, drug abuse history.
- May be allergic to treatment with sorafenib or toripalimab.
- Have received immunotherapy in the past, such as anti-PD-1, anti-PD-L1, anti-PD-L2 drugs, and other drugs that stimulate or co-inhibitory T cell receptors (such as CTLA-4, OX- 40 or CD137) treatment
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- Severe mental or nervous system disorders that affect informed consent and/or expression or perception of adverse events.
- Previous clinical diagnosis of hepatic encephalopathy in the past 6 months. Patients with hepatic encephalopathy which are controlled by rifaximin or lactulose are not allowed to participate in the study.
- Moderate to severe ascitic fluid with obvious symptoms.
- Concomitant secondary malignant tumors or other tumors (except superficial skin cancer, localized low-grade malignant tumors and carcinoma in situ) within 3 years before the start of the study.
- History of gastrointestinal hemorrhage within 6 months before the start of the study, or was diagnosed by ERCP/CT/DSA as a high risk of rupture and bleeding of esophageal gastric varices.
- Suffer from serious unhealed wounds, ulcers or fractures.
- Active central nervous system metastasis or cancerous meningitis.
- Active tuberculosis (TB), who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before the first medication.
- History of biliary fistula, gastrointestinal perforation, and intra-abdominal abscess within 4 weeks before the start of the study.
- History of unstable angina, myocardial infarction, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack, pulmonary embolism) within 3 months before the start of the study.
- NCI-CTCAE v.4 grade ≥2 cardiac arrhythmia, atrial fibrillation, or QT interval prolongation of any NCI-CTCAE v.4 grade (male > 450ms, female > 470ms).
- Uncontrollable hypertension treated with best antihypertensive drugs (> 150/90mmHg after rational medication).
- History of HIV infection.
- Females who are pregnant or breastfeeding.
- Live vaccines were vaccinated within 30 days before the first dose of study drug. Live vaccines include but are not limited to the following: measles, mumps, rubella, varicella/shingles (chickenpox), yellow fever, rabies, BCG (BCG) and typhoid vaccines. Since seasonal influenza vaccines for injection are usually inactivated virus vaccines, their use is allowed; however, intranasal influenza vaccines (for example, FluMist) are live attenuated vaccines, so they are not allowed.
- Have an active autoimmune disease that requires systemic treatment in the past 2 years (for example, immunomodulatory drugs, corticosteroids, or immunosuppressive drugs. Autoimmune diseases such as autoimmune hepatitis, interstitial pneumonia, uveal Inflammation, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, Glomerulonephritis, etc., hyperthyroidism or hypothyroidism, asthma that requires bronchodilator treatment, etc.). Replacement therapy (for example, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic therapy and is allowed.
- Combined with medical contraindications that cannot accept any contrast-enhanced imaging examinations (CT or MRI).
- Severely allergic to research intervention and/or any of its excipients (≥Grade 3).
- Uncontrolled metabolic disorders or other non-malignant tumor organs or systemic diseases or cancer secondary reactions, which can lead to higher medical risks and/or uncertainty in survival evaluation.
- Patients who have received allogeneic tissue/solid organ transplantation.
- Patients with other acute or chronic diseases, mental illnesses, or abnormal laboratory test values that may cause the following results: increase the risk related to study participation or study drug administration, or interfere with the interpretation of the study results, and the patients shall be treated according to the judgment of the investigator classified as not eligible to participate in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Randomized Clinical Trial of Radiotherapy Plus Toripalimab Versus Sorafenib in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis
To explore the efficacy of radiotherapy plus toripalimab Versus standard treatment of sorafenib in advanced hepatocellular carcinoma with Portal Vein/Hepatic vein Tumor Thrombosis.
Read the detailed description
This is an single-center, open, randomized study, which is going to enroll patients filtered to meet the standard of advanced hepatocellular carcinoma, in a 2: 1-proportional randomly assigned to the test group and control group. Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity-modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy started. Patients in the control group will be treated with sorafenib (400mg, twice a day).
- Being tested
- Radiotherapy plus Toripalimab, Sorafenib
- Keywords
- Radiotherpay, Anti-PD-1 antibody, Advanced Hepatocellular Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy plus ToripalimabOther
Intensity modulated radiotherapy has shown important role in the treatment of hepatocellular carcinoma (HCC), especially for advanced disease with portal vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis. Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2).
SorafenibDrug
Sorafenib is a multi-targeted oral drug for the treatment of cancer.Treatment of inoperable advanced renal cell carcinoma ,inoperable or distant metastatic primary hepatocellular carcinoma and so on.
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy plus Toripalimab | Experimental | Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy. Receives: Other: Radiotherapy plus Toripalimab |
| Sorafenib | Active comparator | Patients in the control group will be treated with sorafenib (400mg, twice a day). Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
TTP
Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death.
Measured: up to 24 months
Secondary outcomes (3)
ORR
Overall Response Rate (ORR) was defined as the total of CR (Complete Response) and PR (Partial Response). CR and PR were assessed by independent reviewers according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: up to 24 months
OS
Overall Survival (OS) was defined as the duration from the date of patient recruited to the date of death with any reason.
Measured: up to 24 months
Incidence of grade 3 and above adverse events
Adverse events was evaluated during received protocol therapy according to CTCAE 4.03.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2021
- Study start2 Mar 2021
- Primary completion27 Dec 2024
- Study completion5 Feb 2025
Why it stopped: IDMC recommended to terminate the study since Interim analysis showed that the experimental group had significant superiority over the control group in TTP and OS (p\<0.001), meeting the predefined interim analysis endpoints in the study protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RadiotherapyStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, BO CHEN, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04709380
- Sponsor's protocol ID
- NCC2509
- Status last verified
- Feb 2025
- First submitted
- 13 Jan 2021
- Last updated
- 26 Feb 2025
- 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 26 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized Clinical Trial of Radiotherapy Plus Toripalimab Versus Sorafenib in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis
- ClinicalTrials.gov ID
- NCT04709380
- Acronym / sponsor ID
- NCC2509
- Keywords
- Radiotherpay, Anti-PD-1 antibody, Advanced Hepatocellular Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IDMC recommended to terminate the study since Interim analysis showed that the experimental group had significant superiority over the control group in TTP and OS (p\<0.001), meeting the predefined interim analysis endpoints in the study protocol.
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 2 Mar 2021 (actual)
- Primary completion
- 27 Dec 2024 (actual)
- Study completion
- 5 Feb 2025 (actual)
- First posted
- 14 Jan 2021 (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.
To explore the efficacy of radiotherapy plus toripalimab Versus standard treatment of sorafenib in advanced hepatocellular carcinoma with Portal Vein/Hepatic vein Tumor Thrombosis.
Detailed description
This is an single-center, open, randomized study, which is going to enroll patients filtered to meet the standard of advanced hepatocellular carcinoma, in a 2: 1-proportional randomly assigned to the test group and control group. Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity-modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy started. Patients in the control group will be treated with sorafenib (400mg, twice a day).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy plus Toripalimab | Experimental | Other: Radiotherapy plus ToripalimabPatients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy. |
| Sorafenib | Active comparator | Drug: SorafenibPatients in the control group will be treated with sorafenib (400mg, twice a day). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Clinical or histologic diagnosis of Hepatocellular carcinoma (HCC) according to the 2019 version of liver cancer diagnosis and treatment guideline.
- Aged between 18 and 80 years.
- ECOG 0-1.
- The left volume of liver-GTV which is received less than dose of 5Gy is more than 250ml after the portal vein/hepatic vein tumor thrombosis and its connected primary main lesion is received treatment dose of 40-60Gy/10-20f.
- Patients may have a history of treatments for hepatocellular carcinoma such as TACE, radiofrequency, surgery, chemotherapy, and Chinese herbal medicine, but all patients must have not been received targeted therapy and Immunotherapy, such as anti-PD-1, anti-PD-L1 or anti-PD-L2 drug therapy.
Key exclusion criteria (27 listed)
- Those who are participating in other clinical trials.
- Had prior abdominal irradiation, or had prior liver transplantation.
- Patients with chronic, serious diseases such as cardiac, pulmonary, and renal disease.
- Suspected or true alcohol, drug abuse history.
- May be allergic to treatment with sorafenib or toripalimab.
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 |
|---|---|---|
| Radiotherapy plus ToripalimabIntensity modulated radiotherapy has shown important role in the treatment of hepatocellular carcinoma (HCC), especially for advanced disease with portal vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis. Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2). | Other | Radiotherapy plus Toripalimab |
| SorafenibSorafenib is a multi-targeted oral drug for the treatment of cancer.Treatment of inoperable advanced renal cell carcinoma ,inoperable or distant metastatic primary hepatocellular carcinoma and so on. | Drug | Sorafenib |
Primary outcome
TTP
Time frame: up to 24 months
Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death.
3 secondary outcomes
ORR
Time frame: up to 24 months
OS
Time frame: up to 24 months
Incidence of grade 3 and above adverse events
Time frame: up to 24 months
Results and safety
The study was stopped early (reason given: IDMC recommended to terminate the study since Interim analysis showed that the experimental group had significant superiority over the control group in TTP and OS (p\<0.001), meeting the predefined interim analysis endpoints in the study protocol.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2025.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radiotherapy plus Toripalimab and Sorafenib in people with Radiotherapy and Toripalimab, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences 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 15 inclusion and 27 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: stopped early, as of the sponsor's last update on 26 Feb 2025. 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 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?
The study was stopped early (reason given: IDMC recommended to terminate the study since Interim analysis showed that the experimental group had significant superiority over the control group in TTP and OS (p\<0.001), meeting the predefined interim analysis endpoints in the study protocol.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TTP (time frame: up to 24 months). 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 26 Feb 2025.