Hepatocellular CarcinomaPhase 2T-DoubleNCT04796025
TACE Combined With Sintilimab Plus Bevacizumab Biosimilar in Hepatocellular Carcinoma (BCLC-C Stage ): a Prospective Single-arm Phase II Clinical Study
A Phase 2 study testing Sintilimab; Bevacizumab Biosimilar in people with Hepatocellular Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with pd-1 antibody immunotherapy (Sintilimab) and anti-VEGF (Bevacizumab Biosimilar) in patients with advanced hepatocellular carcinoma (BCLC-C Stage). Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Sintilimab; Bevacizumab Biosimilar
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteChina
- Study dates
- 23 Sep 2021to 31 Aug 2024
- 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient voluntarily joined the study and signed an informed consent form;
- ≥18 and ≤69 years old, both male and female;
- Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma (unresectable or metastatic), at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm);
- Child-Pugh score ≤ 6 points (Child-Pugh A);
- BCLC staging is stage C; PVTT classification is combined with PVTT (program classification PVTT ≤ 3), and a single lesion in the liver (or multiple lesions with diameter) ≤ 7cm of primary liver cancer.
- Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past;
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- ECOG score: 0～1 (see Annex 1 for ECOG scoring criteria);
- Expected survival period ≥ 12 weeks;
- The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration):
- The absolute count of neutrophils≥1.5×109/L; Platelet ≥80×109/L; Hemoglobin ≥90 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤1.5×ULN (within 7 days before the first administration); ALT and AST ≤3×ULN (within 7 days before the first dose); AKP≤ 2.5×ULN; Serum creatinine≤1.5×ULN;
- Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, Carelil should be given during the trial and at the last time Use effective methods for contraception within 3 months after the onslumab.
Who cannot join
- The patient has any active autoimmune disease or a history of autoimmune disease;
- The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
- The number of system treatment lines ≥ 2 lines;
- Severe allergic reaction to other monoclonal antibodies;
- Those with a known history of central nervous system metastasis or hepatic encephalopathy;
- Patients whose liver tumor burden is greater than 50% of the total liver volume, or who have received liver transplantation in the past;
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- Ascites with clinical symptoms, those who need puncture, drainage, or those who have received ascites drainage within the past 3 months, except those who have only a small amount of ascites on imaging but not accompanied by clinical symptoms;
- Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
- Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc>450ms (male); QTc>470ms (female);
- Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
- Significant clinically significant bleeding symptoms or clear bleeding tendency occurred within 3 months before randomization, such as pertussis/hemoptysis 2.5ml or more, gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic stomach Ulcer or vasculitis, etc., if the stool occult blood is positive at the baseline, it can be re-examined. If it is still positive after the re-examination, a gastroscopy is required. If the gastroscope shows severe esophageal and gastric varices, it cannot be included in the group (3 before the group) Except those who have undergone gastroscopy within a month or less to exclude such cases);
- Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g;
- Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication <5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1;
- The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count >15×109/L; Patients with congenital or acquired immune deficiencies (such as HIV-infected persons);
- Patients with HBV DNA>2000 IU/ml (or 104 copies/ml), HCV RNA>103 copies/ml, HBsAg+ and anti-HCV antibody positive;
- The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
- Patients with bone metastases who received palliative radiotherapy within 4 weeks before participating in the study >5% of the bone marrow area;
- The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy;
- Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period;
- According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and serious laboratory tests 22. Abnormalities, accompanied by family or social factors, will affect the safety 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
Fei Gao, PhD, MD, 86-020-87343907, gaof@sysucc.org.cn
Zhenakng Qiu, MD, 86-020-87343895, qiuzk@sysucc.org.cn
About this study
Official title: Sun Yat-sen University Cancer Center
The purpose of this study is to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with pd-1 antibody immunotherapy (Sintilimab) and anti-VEGF (Bevacizumab Biosimilar) in patients with advanced hepatocellular carcinoma (BCLC-C Stage).
Read the detailed description
This is a prospective, single arm, phase II study to evaluate the efficacy and safety of TACE combined with Sintilimab and Bevacizumab Biosimilar (T-Double Therapy) in patients with HCC (BCLC-C Stage). Subjects who meet the admission criteria will be treated with Sintilimab and Bevacizumab Biosimilar after TACE until disease progression, intolerable toxicity, death, withdrawal of the patient or the researchers determined that the drug must be discontinued.
The primary outcome measure is to evaluate the objective response rate (ORR) of T-Double Therapy for advanced HCC (BCLC C-stage). The secondary outcome measures include the duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) in 6- and 12-months, overall survival rate (OSR) in 6- and 12-months, the median progression-free survival time (mPFS) and median overall survival time (mOS) of T-Double Therapy for advanced HCC. This study also aims to assess the safety and adverse reactions of T-Double Therapy for advanced HCC.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Sintilimab; Bevacizumab Biosimilar
- Keywords
- TACE, Sintilimab, Bevacizumab Biosimilar, Hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sintilimab; Bevacizumab BiosimilarDrug
Also called TACE
1-4 cycles, intra-arterial infusion: sindilimab 200mg + bevacizumab 7.5mg/kg, q3w; 5-18 cycles: Sintilimab (200mg ivdrip D1 Q3W)+Bevacizumab Biosimilar (15mg/kg ivdrip D1 Q3W）
| Study group | Role | What they receive |
|---|---|---|
| T-Double | Experimental | TACE Combined With Sintilimab Plus Bevacizumab Biosimilar Receives: Drug: Sintilimab; Bevacizumab Biosimilar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) by RECIST 1.1 and mRECIST
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST
Measured: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
Secondary outcomes (6)
Disease control rate (DCR)
DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST.
Measured: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
Duration of response (DOR) by RECIST 1.1 and mRECIST
DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1 and mRECIST
Measured: From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to 2 years)
Progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST
PFSR in 6- and 12-months
Measured: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to 2 years)
Overall survival rate (OSR)
OSR in 6- and 12-months
Measured: From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)
Progression-free survival time (mPFS)
The progression-free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1 and mRECIST.
Measured: From date of first dose of study drug to the date of first documentation of disease progression (up to 2 years)
Median overall survival time (mOS)
OS is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.
Measured: From the start date of the Treatment Phase until date of death from any cause (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2021
- Study start23 Sep 2021
- Primary completion31 Aug 2023 (estimated)
- Study completion31 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fei Gao, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04796025
- Sponsor's protocol ID
- T-Double
- Acronym
- T-Double
- Status last verified
- Sep 2021
- First submitted
- 10 Mar 2021
- Last updated
- 28 Sep 2021
- Results posted
- 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 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sun Yat-sen University Cancer Center
- ClinicalTrials.gov ID
- NCT04796025
- Acronym / sponsor ID
- T-Double / T-Double
- Conditions
- Hepatocellular Carcinoma
- Keywords
- TACE, Sintilimab, Bevacizumab Biosimilar, Hepatocellular carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 31 Aug 2023 (estimated)
- Study completion
- 31 Aug 2024 (estimated)
- First posted
- 12 Mar 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.
The purpose of this study is to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with pd-1 antibody immunotherapy (Sintilimab) and anti-VEGF (Bevacizumab Biosimilar) in patients with advanced hepatocellular carcinoma (BCLC-C Stage).
Detailed description
This is a prospective, single arm, phase II study to evaluate the efficacy and safety of TACE combined with Sintilimab and Bevacizumab Biosimilar (T-Double Therapy) in patients with HCC (BCLC-C Stage). Subjects who meet the admission criteria will be treated with Sintilimab and Bevacizumab Biosimilar after TACE until disease progression, intolerable toxicity, death, withdrawal of the patient or the researchers determined that the drug must be discontinued.
The primary outcome measure is to evaluate the objective response rate (ORR) of T-Double Therapy for advanced HCC (BCLC C-stage). The secondary outcome measures include the duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) in 6- and 12-months, overall survival rate (OSR) in 6- and 12-months, the median progression-free survival time (mPFS) and median overall survival time (mOS) of T-Double Therapy for advanced HCC. This study also aims to assess the safety and adverse reactions of T-Double Therapy for advanced HCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| T-Double | Experimental | Drug: Sintilimab; Bevacizumab BiosimilarTACE Combined With Sintilimab Plus Bevacizumab Biosimilar |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- The patient voluntarily joined the study and signed an informed consent form;
- ≥18 and ≤69 years old, both male and female;
- Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma (unresectable or metastatic), at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm);
- Child-Pugh score ≤ 6 points (Child-Pugh A);
- BCLC staging is stage C; PVTT classification is combined with PVTT (program classification PVTT ≤ 3), and a single lesion in the liver (or multiple lesions with diameter) ≤ 7cm of primary liver cancer.
Key exclusion criteria (21 listed)
- The patient has any active autoimmune disease or a history of autoimmune disease;
- The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
- The number of system treatment lines ≥ 2 lines;
- Severe allergic reaction to other monoclonal antibodies;
- Those with a known history of central nervous system metastasis or hepatic encephalopathy;
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 |
|---|---|---|
| Sintilimab; Bevacizumab BiosimilarAlso: TACE1-4 cycles, intra-arterial infusion: sindilimab 200mg + bevacizumab 7.5mg/kg, q3w; 5-18 cycles: Sintilimab (200mg ivdrip D1 Q3W)+Bevacizumab Biosimilar (15mg/kg ivdrip D1 Q3W） | Drug | T-Double |
Primary outcome
Objective response rate (ORR) by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST
6 secondary outcomes
Disease control rate (DCR)
Time frame: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
Duration of response (DOR) by RECIST 1.1 and mRECIST
Time frame: From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to 2 years)
Progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to 2 years)
Overall survival rate (OSR)
Time frame: From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)
Progression-free survival time (mPFS)
Time frame: From date of first dose of study drug to the date of first documentation of disease progression (up to 2 years)
Median overall survival time (mOS)
Time frame: From the start date of the Treatment Phase until date of death from any cause (up to 2 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- 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 Sintilimab; Bevacizumab Biosimilar 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 11 inclusion and 21 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 28 Sep 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 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 Fei Gao, M.D. (86-13760869828, gaof@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) by RECIST 1.1 and mRECIST (time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 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 28 Sep 2021.