BCLC Stage B Hepatocellular CarcinomaPhase 2NCT04204577
The Safety and Efficacy of Thermal Ablation Combined With Apatinib and Carilimub for Advanced Liver Cancer
A Phase 2 study testing Apatinib Mesylate in people with BCLC Stage B Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
The purpose of this study was to evaluate the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for the treatment of advanced liver cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma
- What is being tested?
- Apatinib Mesylate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2019to Nov 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18-80 years old;
- Patients with primary hepatocellular carcinoma who are strictly in accordance with the clinical diagnostic criteria for the diagnosis and treatment of primary liver cancer (2017 edition) or confirmed by histopathology or cytology;
- Child-Pugh A or B;
- BCLC B-C;
- Eastern Cooperative Oncology Group(ECOG) body condition within a week before enrollment score 0-2;
- Life expectancy of at least 3 months;
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- Adequate main organ function:
- Hemoglobin ≥90g/L. Absolute neutrophil count (ANC) ≥1,500/mm3. Platelets ≥50,000/ul. Albumin ≥29g/L. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <3 the upper limit of normal (ULN). Total bilirubin (TBIL) ≤1.5 ULN. Creatinine ≤1.5 ULN.
- Women of childbearing age (generally 15-49 years of age) are required to have a negative pregnancy test (serum or urine) within 14 days prior to enrollment, and will voluntarily use the appropriate method of contraception during the observation period and within 8 weeks after the last administration of the study drug; For men, appropriate methods of contraception should be used during the observation period and within 8 weeks after the last administration of the study drug.
- Be willing and able to provide written informed consent for the study.
Who cannot join
- History of liver transplantation.
- Other anti-angiogenic drugs and (or PD-1) antibody drugs were used within 3 months prior to enrollment.
- History of immunosuppressive drugs used for 14 days prior to the first use of SHR-1210, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid hormones(no more than 10 mg/day of turpentine or equivalent) Pharmacological doses of other corticosteroids) .
- Subjects are allergic to Apatinib Mesylate Tablets, SHR-1210, pharmaceutical excipients, or other monoclonal antibodies.
- Attenuated Live Vaccine in four weeks before study or during study.
- Uncontrolled or symptomatic active central nervous system (CNS) metastases are known to present with clinical signs, cerebral edema, spinal cord compression, cancerous meningitis, pia mater disease, and/or progressive growth. Patients with a history of central nervous system metastasis or spinal cord compression who have been treated and who have been clinically stable after 4 weeks of discontinuation of anticonvulsants and steroids prior to the study's first dose may be enrolled in the study.
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- Peripheral neuropathy grade >1.
- There are any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, Hyperthyroidism, decreased thyroid function; subjects with vitiligo or complete remission in childhood asthma, can be included without adult intervention after adult; asthma requiring medical intervention for bronchodilators cannot be included).
- History of human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV-DNA≥1000 IU/ml), hepatitis C (positive hepatitis C antibody, and higher HCV-RNA than the lower limit of detection of the analytical method) or in combination with hepatitis B and hepatitis C, patients requiring antiviral therapy during the study;
- Cardiovascular disease with 6 months before enrollment: Myocardial infarction, severe/unstable angina, NYHA class 2 or higher cardiac dysfunction, poorly controlled arrhythmias (including QTcF interval men >450 ms, women >470 ms, QTcF interval calculated by Fridericia formula), symptomatic hyperemia Sexual heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism)
- High blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90 mmHg)
- Abnormal coagulation (INR >1.5×ULN or activated partial thromboplastin time (APTT) >1.5×ULN), with bleeding tendency or receiving thrombolysis or anticoagulant therapy.
- Hereditary or acquired bleeding and thrombosis trends, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.
- Obvious hemoptysis in the first 2 months before the study or daily hemoptysis exceed 2.5ml.
- Significant clinically bleeding symptoms or clear bleeding tendency within 3 months prior to the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood (++) and above, or vasculitis.
- Artery/ venous thrombosis, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism,etc.
- Long-term anticoagulant therapy with warfarin or heparin or antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).
- Severe infection within 4 weeks prior to first drug administration (eg, intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever >38.5℃ during screening period/first drug administration.
- History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Participated in any other drug clinical study within 4 weeks prior to first drug administration , or no more than 5 half-lives from the last study.
- History of psychotropic substance abuse or drug abuse.
- Serious physical or mental illness, laboratory abnormalities, increasing risk of participating in the study, interfere with the results of the study, and patients considered by the investigator to be unfit for the study.
Trial locations and contacts
1 site in 1 country.
Xin Li contact
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Jie Yu, Doctor, 8601066939530, yu-jie301@hotmail.com
About this study
Official title: Three-arm Open Parallel Control Phase II Trial for Evaluation of Thermal Ablation Combined With Apatinib and PD-1 Antibody SHR-1210 for Advanced Liver Cancer
The purpose of this study was to evaluate the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for the treatment of advanced liver cancer.
Read the detailed description
Primary liver cancer is a common malignant tumor in the world. Its pathogenesis is concealed and clinically asymptomatic. It is mostly in the middle and late stages of the disease. It is often combined with different degrees of cirrhosis. The liver function reserve is poor.About 80% of patients are in the first place. The operation has been lost at the time of diagnosis.
Primary liver cancer is not sensitive to conventional treatments such as radiotherapy and chemotherapy because of its unique tissue type. For advanced liver cancer, ablation combined with other systemic treatments is expected to alleviate the patient's condition, prolong the patient's survival time, and benefit more patients. The long-term clinical efficacy of tumor thermal ablation has been reported more, the basic conclusion is consistent, hat is, the 5-year survival rate of early stage tumors such as liver cancer less than 3cm is not inferior to surgical resection, or even better. Liver cancer is rich in blood supply and tumor blood vessels are dense. The formation and maintenance of these blood vessels requires pro-angiogenic signals, of which VEGFR is a key component. Apatinib is a small molecule tyrosine kinase inhibitor that inhibits VEGFR at very low concentrations. SHR-1210 is a humanized anti-programmed cell death receptor 1 antibody.
This study was designed to evaluate the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for the treatment of advanced liver cancer.
- Being tested
- Apatinib Mesylate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apatinib MesylateDrug
Also called SHR-1210
Evaluation of the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for advanced liver cancer.
| Study group | Role | What they receive |
|---|---|---|
| Thermal ablation | No intervention | Taking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease. |
| Thermal ablation combined with apatinib | Experimental | Taking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease.
Oral apatinib mesylate tablets, 250 mg, orally once a day. Take about half an hour after a meal (the daily dose should be as much as possible), and take it with warm water. Apatinib was discontinued 7 days before each thermal ablation treatment, and after the thermal ablation treatment, the patient's aminotransferase returned to normal and continued to take apatinib. Receives: Drug: Apatinib Mesylate |
| Ablation combined with apatinib and PD-1 antibody SHR-1210 | Experimental | Taking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease.
Oral apatinib mesylate tablets, 250 mg, orally once a day. Take it with warm water about half an hour after a meal (the daily dose should be as much as possible). Apatinib was discontinued 7 days before each thermal ablation treatment, and after the thermal ablation treatment, the patient's aminotransferase returned to normal and continued to take apatinib.
SHR-1210, 200mg, intravenous infusion for 30 minutes (including the time of the tube,the overall infusion time is not shorter than 20 minutes, no longer than 60 minutes), once every 2 weeks; the first dose with the apatite Simultaneous administration of PD, PD-1 injection is not affected by thermal ablation. Receives: Drug: Apatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free-Survival(PFS)
The period between the onset of treatment from the onset of treatment, the observation of disease progression, or the death of any cause.
Measured: Up to two years
Secondary outcomes (6)
Objective response rate (ORR) according to RECIST 1.1
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period.
Measured: Up to approximately two years
Disease control rate(DCR)
The proportion of patients who had a best response rating of complete response， partial response, or stable disease.
Measured: Up to approximately two years
Overall survival(OS)
Overall survival is defined as time from the start of treatment until death due to any reason.
Measured: Up to approximately two years
Overall survival rate of 6 months and 12 months
Overall survival rate of 6 months and 12 months.
Measured: 6 months and 12 months
Safety: incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03
The incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03
Measured: Up to approximately two years
Quality of life score(QOL)
Quality of life score(QOL)0-100
Measured: Up to approximately two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2019
- Study start1 Nov 2019
- Primary completionNov 2021 (estimated)
- Study completionNov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BCLC Stage B Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Chinese PLA General 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ping Liang, Chinese PLA General Hospital
- Investigators
- Jie Yu, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04204577
- Sponsor's protocol ID
- S2019-128-02
- Status last verified
- Dec 2019
- First submitted
- 28 Aug 2019
- Last updated
- 19 Dec 2019
- 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 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Three-arm Open Parallel Control Phase II Trial for Evaluation of Thermal Ablation Combined With Apatinib and PD-1 Antibody SHR-1210 for Advanced Liver Cancer
- ClinicalTrials.gov ID
- NCT04204577
- Acronym / sponsor ID
- S2019-128-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- Nov 2021 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 19 Dec 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.
The purpose of this study was to evaluate the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for the treatment of advanced liver cancer.
Detailed description
Primary liver cancer is a common malignant tumor in the world. Its pathogenesis is concealed and clinically asymptomatic. It is mostly in the middle and late stages of the disease. It is often combined with different degrees of cirrhosis. The liver function reserve is poor.About 80% of patients are in the first place. The operation has been lost at the time of diagnosis.
Primary liver cancer is not sensitive to conventional treatments such as radiotherapy and chemotherapy because of its unique tissue type. For advanced liver cancer, ablation combined with other systemic treatments is expected to alleviate the patient's condition, prolong the patient's survival time, and benefit more patients. The long-term clinical efficacy of tumor thermal ablation has been reported more, the basic conclusion is consistent, hat is, the 5-year survival rate of early stage tumors such as liver cancer less than 3cm is not inferior to surgical resection, or even better. Liver cancer is rich in blood supply and tumor blood vessels are dense. The formation and maintenance of these blood vessels requires pro-angiogenic signals, of which VEGFR is a key component. Apatinib is a small molecule tyrosine kinase inhibitor that inhibits VEGFR at very low concentrations. SHR-1210 is a humanized anti-programmed cell death receptor 1 antibody.
This study was designed to evaluate the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for the treatment of advanced liver cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Thermal ablation | No intervention | –Taking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease. |
| Thermal ablation combined with apatinib | Experimental | Drug: Apatinib MesylateTaking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease. Oral apatinib mesylate tablets, 250 mg, orally once a day. Take about half an hour after a meal (the daily dose should be as much as possible), and take it with warm water. Apatinib was discontinued 7 days before each thermal ablation treatment, and after the thermal ablation treatment, the patient's aminotransferase returned to normal and continued to take apatinib. |
| Ablation combined with apatinib and PD-1 antibody SHR-1210 | Experimental | Drug: Apatinib MesylateTaking standard thermal ablation treatment. Its specific number and time interval depend on the patient's own condition and disease. Oral apatinib mesylate tablets, 250 mg, orally once a day. Take it with warm water about half an hour after a meal (the daily dose should be as much as possible). Apatinib was discontinued 7 days before each thermal ablation treatment, and after the thermal ablation treatment, the patient's aminotransferase returned to normal and continued to take apatinib. SHR-1210, 200mg, intravenous infusion for 30 minutes (including the time of the tube,the overall infusion time is not shorter than 20 minutes, no longer than 60 minutes), once every 2 weeks; the first dose with the apatite Simultaneous administration of PD, PD-1 injection is not affected by thermal ablation. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age between 18-80 years old;
- Patients with primary hepatocellular carcinoma who are strictly in accordance with the clinical diagnostic criteria for the diagnosis and treatment of primary liver cancer (2017 edition) or confirmed by histopathology or cytology;
- Child-Pugh A or B;
- BCLC B-C;
- Eastern Cooperative Oncology Group(ECOG) body condition within a week before enrollment score 0-2;
Key exclusion criteria (22 listed)
- History of liver transplantation.
- Other anti-angiogenic drugs and (or PD-1) antibody drugs were used within 3 months prior to enrollment.
- History of immunosuppressive drugs used for 14 days prior to the first use of SHR-1210, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid hormones(no more than 10 mg/day of turpentine or equivalent) Pharmacological doses of other corticosteroids) .
- Subjects are allergic to Apatinib Mesylate Tablets, SHR-1210, pharmaceutical excipients, or other monoclonal antibodies.
- Attenuated Live Vaccine in four weeks before study or during study.
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 |
|---|---|---|
| Apatinib MesylateAlso: SHR-1210Evaluation of the efficacy and safety of simple local ablation, local ablation combined with apatinib, local ablation combined with apatinib and PD-1 antibody SHR-1210 for advanced liver cancer. | Drug | Ablation combined with apatinib and PD-1 antibody SHR-1210, Thermal ablation combined with apatinib |
Primary outcome
Progression-Free-Survival(PFS)
Time frame: Up to two years
The period between the onset of treatment from the onset of treatment, the observation of disease progression, or the death of any cause.
6 secondary outcomes
Objective response rate (ORR) according to RECIST 1.1
Time frame: Up to approximately two years
Disease control rate(DCR)
Time frame: Up to approximately two years
Overall survival(OS)
Time frame: Up to approximately two years
Overall survival rate of 6 months and 12 months
Time frame: 6 months and 12 months
Safety: incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03
Time frame: Up to approximately two years
Quality of life score(QOL)
Time frame: Up to approximately two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
- 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.
Xin Li contact
Jie Yu principal investigator
Chinese PLA General Hospital
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 Apatinib Mesylate in people with BCLC Stage B Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by Chinese PLA General 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 10 inclusion and 22 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 19 Dec 2019. 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 Jie Yu (8601066939530, yu-jie301@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free-Survival(PFS) (time frame: Up to two 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 19 Dec 2019.