Hepatocellular Carcinoma Non-resectablePhase 3NCT05985798
Sintilimab+Bevacizumab+TACE vs. Lenvatinib+TACE for Advanced HCC
A Phase 3 study testing Sin-Bev-TACE and Len-TACE in people with Hepatocellular Carcinoma Non-resectable, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This study is conducted to evaluate the efficacy and safety of sintilimab, bevacizumab plus TACE (Sin-Bev-TACE) compared with lenvatinib plus TACE (Len-TACE) for patients with advanced stage hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma Non-resectable
- What is being tested?
- Sin-Bev-TACE and Len-TACE
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 258 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2023to 31 Jul 2027
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced HCC (BCLC stage C) with diagnosis confirmed pathologically or clinically
- Disease amenable to TACE
- No prior systemic therapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
- Child-Pugh class A
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
- Life expectancy of at least 3 months
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- At least one measurable intrahepatic lesion
- Adequate organ and hematologic function
- Patients with active hepatitis B are allowed, but they need to receive antiviral treatment to achieve a HBV DNA<10^2 IU/mL
- Patients with hepatitis C need to finish the anti-HCV treatment
Who cannot join
- Tumor thrombus involving main portal vein or both the first left and right branch of portal vein
- Vena cava invasion
- Central nervous system metastasis
- History of hepatic encephalopathy
- History of organ and cell transplantation
- Uncontrolled ascites, hydrothorax or pericardial effusion
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- Prior esophageal and/or gastric varices bleeding within 6 months prior to initiation of study treatment
- Presence of known severe (G3) varicose veins in endoscopy within 3 months before the first dose. Evidence of portal hypertension (including the finding of splenomegaly in imaging studies) with a high risk of bleeding assessed by the investigator
- Presence of any life-threatening bleeding events within the past 3 months, including the need for transfusion, surgery or local treatment, and continuous medication therapy
- Any arterial or venous thromboembolic events within 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of serious thromboembolism. Presence of implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, barring stable thrombosis following the conventional anticoagulation treatment. Prophylactic use of low-dose low-molecular-weight heparin (e.g., enoxaparin 40 mg/day) is permitted.
- A 10-day consecutive dosing of aspirin (> 325 mg/day) or other drugs, e.g., dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeks before the first dose
- Uncontrolled hypertension after the optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
- Symptomatic congestive cardiac failure (NYHA Class II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500 ms (calculated using Fridericia formula) during screening
- Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic therapy
- History of gastrointestinal perforation and/or fistula, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection accompanied with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months
- History or current experience of pulmonary fibrosis and such lung diseases as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, and severely impaired lung function
- Active tuberculosis (TB), currently receiving anti-tuberculosis treatment or received such treatment within 1 year before the first dose
- Human immunodeficiency virus (HIV) infected (HIV 1/2 antibody positive) and known syphilis infection requiring treatment
- Active or poorly clinically controlled serious infections. Severe infections within 4 weeks before the first dose, including but not limited to hospitalization caused by infection, bacteremia, or severe pneumonia complication
- Presence of active autoimmune diseases requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose. Use of alternative therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is permitted. Known history of primary immunodeficiency diseases. For patients with positive autoimmune antibodies only, they should be assessed by the investigator to determine whether they had an autoimmune disease
- Receipt of immunosuppressants within 4 weeks before the first dose, excluding local glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or equivalents), while the temporary use of glucocorticoids for preventing allergies or treating dyspneic symptoms of such diseases as asthma and chronic obstructive pulmonary disease is permitted
- Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of tissue biopsy or other minor surgeries within 7 days before the first dose, barring venipuncture and catheterization for intravenous infusion.
- Receipt of systemic treatment with traditional Chinese medicines with cancer indications or immunomodulators (including thymosin, interferon, and interleukin, barring local use for controlling pleural fluid or ascites) within 2 weeks before the first dose
- History of malignancy other than HCC
- Known hypersensitivity to any ingredients in sintilimab, bevacizumab and lenvatinib preparations or previous severe hypersensitivity reactions to other monoclonal antibodies
- Pregnant or breastfeeding female patients
- Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that may lead to the following consequences: increased study participation or drug-related risks, or interference with interpreting trial results, and considered ineligible for participating in the trial by the investigator
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
the Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510260
Mingyue Cai, Dr., +86-20-34156205, cai020@yeah.net
Kangshun Zhu, Dr., +86-20-34156205, zhksh010@163.com
About this study
Official title: Sintilimab, Bevacizumab Plus TACE Versus Lenvatinib Plus TACE for Advanced Stage Hepatocellular Carcinoma: A Randomized Controlled Trial
This study is conducted to evaluate the efficacy and safety of sintilimab, bevacizumab plus TACE (Sin-Bev-TACE) compared with lenvatinib plus TACE (Len-TACE) for patients with advanced stage hepatocellular carcinoma (HCC).
Read the detailed description
This is a multicenter, prospective and randomized controlled trial to evaluate the efficacy and safety of Sin-Bev-TACE versus Len-TACE for patient with advanced HCC.
258 patients with advanced HCC (BCLC C stage) will be enrolled in this study. The patients will receive either sintilimab and bevacizumab (Sin-Bev) or lenvatinib (Len) after first TACE using an 1:1 randomization scheme. In the Sin-Bev-TACE arm, sintilimab (200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) will be started at 3-7 days after the first TACE. In the the Len-TACE arm, lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at 3-7 days after the first TACE.
TACE will be repeated on demand based on the evaluation of follow-up laboratory and imaging examination. Sintilimab and bevacizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Lenvatinib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. In the Sin-Bev-TACE arm, patients will be allowed to have sintilimab or bevacizumab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.
The primary end point of this study is overall survival (OS). The secondary endpoints are progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Being tested
- Sin-Bev-TACE, Len-TACE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sin-Bev-TACEDrug
Sintilimab (200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) are administered at 3-7 days after the first TACE. The study treatment of sintilimab and bevacizumab will last up to 24 months. TACE can be repeated on demand.
Len-TACEDrug
Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at 3-7 days after the first TACE. TACE will be repeated on demand.
| Study group | Role | What they receive |
|---|---|---|
| Sin-Bev-TACE | Experimental | Sintilimab, bevacizumab plus TACE Receives: Drug: Sin-Bev-TACE |
| Len-TACE | Active comparator | Lenvatinib plus TACE Receives: Drug: Len-TACE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
The time from date of randomization to death due to any cause.
Measured: 4 years
Secondary outcomes (4)
Progression free survival (PFS)
The time from date of randomization until the first occurrence of disease progression or death due to any cause, whichever occurs first.
Measured: 4 years
Objective response rate (ORR)
The proportion of patients with the best response of complete response (CR) or partial response (PR).
Measured: 4 years
Disease control rate (DCR)
The proportion of patients with the best response of CR, PR, or stable disease (SD).
Measured: 4 years
Adverse Events (AEs)
Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start1 Aug 2023
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma Non-resectableStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Guangzhou Medical 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 258 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Affiliated Hospital of Guangdong Medical University, Zhongshan People's Hospital, Guangdong, China, Lecong Hospital, Shunde District, Foshan, First People's Hospital of Foshan, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05985798
- Sponsor's protocol ID
- MIIR-13
- Status last verified
- Aug 2023
- First submitted
- 2 Aug 2023
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sintilimab, Bevacizumab Plus TACE Versus Lenvatinib Plus TACE for Advanced Stage Hepatocellular Carcinoma: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05985798
- Acronym / sponsor ID
- MIIR-13
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 258 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Collaborators
- Affiliated Hospital of Guangdong Medical University, Zhongshan People's Hospital, Guangdong, China, Lecong Hospital, Shunde District, Foshan, First People's Hospital of Foshan, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 14 Aug 2023 (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.
This study is conducted to evaluate the efficacy and safety of sintilimab, bevacizumab plus TACE (Sin-Bev-TACE) compared with lenvatinib plus TACE (Len-TACE) for patients with advanced stage hepatocellular carcinoma (HCC).
Detailed description
This is a multicenter, prospective and randomized controlled trial to evaluate the efficacy and safety of Sin-Bev-TACE versus Len-TACE for patient with advanced HCC.
258 patients with advanced HCC (BCLC C stage) will be enrolled in this study. The patients will receive either sintilimab and bevacizumab (Sin-Bev) or lenvatinib (Len) after first TACE using an 1:1 randomization scheme. In the Sin-Bev-TACE arm, sintilimab (200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) will be started at 3-7 days after the first TACE. In the the Len-TACE arm, lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at 3-7 days after the first TACE.
TACE will be repeated on demand based on the evaluation of follow-up laboratory and imaging examination. Sintilimab and bevacizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Lenvatinib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. In the Sin-Bev-TACE arm, patients will be allowed to have sintilimab or bevacizumab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.
The primary end point of this study is overall survival (OS). The secondary endpoints are progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sin-Bev-TACE | Experimental | Drug: Sin-Bev-TACESintilimab, bevacizumab plus TACE |
| Len-TACE | Active comparator | Drug: Len-TACELenvatinib plus TACE |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Advanced HCC (BCLC stage C) with diagnosis confirmed pathologically or clinically
- Disease amenable to TACE
- No prior systemic therapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
- Child-Pugh class A
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
Key exclusion criteria (27 listed)
- Tumor thrombus involving main portal vein or both the first left and right branch of portal vein
- Vena cava invasion
- Central nervous system metastasis
- History of hepatic encephalopathy
- History of organ and cell transplantation
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 |
|---|---|---|
| Sin-Bev-TACESintilimab (200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) are administered at 3-7 days after the first TACE. The study treatment of sintilimab and bevacizumab will last up to 24 months. TACE can be repeated on demand. | Drug | Sin-Bev-TACE |
| Len-TACELenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at 3-7 days after the first TACE. TACE will be repeated on demand. | Drug | Len-TACE |
Primary outcome
Overall survival (OS)
Time frame: 4 years
The time from date of randomization to death due to any cause.
4 secondary outcomes
Progression free survival (PFS)
Time frame: 4 years
Objective response rate (ORR)
Time frame: 4 years
Disease control rate (DCR)
Time frame: 4 years
Adverse Events (AEs)
Time frame: 4 years
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 14 Aug 2023.
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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.
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 Sin-Bev-TACE and Len-TACE in people with Hepatocellular Carcinoma Non-resectable, run by Second Affiliated Hospital of Guangzhou Medical 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 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: looking for participants now, as of the sponsor's last update on 14 Aug 2023. 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?
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 Mingyue Cai, Dr. (+86-20-34156205, cai020@yeah.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: 4 years). 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 Aug 2023.