Hepatocellular CarcinomaPhase 2NCT03839550
Combine Apatinib Mesylate With PD-1 Antibody SHR-1210 for HCC With High Risk of Recurrence After Radical Resection
A Phase 2 study testing Apatinib Mesylate +SHR-1210 and Hepatic Arterial Infusion(HAI) in people with Hepatocellular Carcinoma, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
The purpose of this study is to assess the efficacy and safety of Apatinib Mesylate combined with PD-1 antibody SHR-1210 in HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT) after radical resection. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Apatinib Mesylate +SHR-1210 and Hepatic Arterial Infusion(HAI)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 15 Feb 2019to 28 Feb 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18-75 years old.
- Patients were primary Hepatocellular carcinoma according to standardization of diagnosis and treatment for Hepatocellular carcinoma(2017 edition)
- The imaging examination confirmed complete response (CR) after 1 month radical surgery ,and consented to postoperative adjuvant therapy
- Preoperative imaging (CT/MRI/PET-CT), intraoperative or postoperative pathology confirmed HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invation(MVI) or secondary and above portal vein branches tumor thrombosis (PVTT) after radical resection.
- Preoperative imaging and perioperative outcomes confirmed no lymph node metastasis and distant metastasis.
- Child-Pugh A.
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- No anti-tumor treatment before radical hepatic resection.
- BCLC A-B
- Eastern Cooperative Oncology Group(ECOG) body condition score 0-1.
- Adequate main organ function:
- Hemoglobin ≥ 90g/L. Absolute neutrophil count (ANC) ≥ 1,500/mm3. Platelets ≥ 100,000/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.
- Tumor rupture or invasion of adjacent organs.
- 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 .
- Subjects are allergic to Apatinib Mesylate Tablets, SHR-1210, pharmaceutical excipients, o other monoclonal antibodies.
- Attenuated Live Vaccine in four weeks before study or during study.
- Uncontrolled or symptomatic active central nervous system (CNS) metastases (if these patients have been treated to clinically stable and discontinuation of anticonvulsants and steroids in four weeks before study may be enrolled).
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- Peripheral neuropathy grade> 1.
- History of autoimmune disease(Subjects with vitiligo or asthma in childhood but complete remission after adult intervention after adulthood may be enrolled)
- Subjectes diagnosed any other malignant tumor within 3 years prior to study, except for adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ
- History of Human Immunodeficiency Virus (HIV).
- Cardiovascular disease: 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.
- Sserious 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.
China1 site
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Hong Zhao, +86-13381106850
About this study
Official title: The Multi-center, Randomized and Controlled Phase II Trail of Apatinib Mesylate Tablets Combined With PD-1 Antibody SHR-1210 for Adjuvant Treatment of Patients With High Recurrence Risk After Radical Operation of Hepatocellular Carcinoma
The purpose of this study is to assess the efficacy and safety of Apatinib Mesylate combined with PD-1 antibody SHR-1210 in HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT) after radical resection. Patients will be randomized 1:1 either to the experimental arm to receive Apatinib Mesylate and PD-1 antibody SHR-1210 or to the standard therapy arm of hepatic arterial infusion(HAI) .
Read the detailed description
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, which is the third cause of cancer related deaths. Radical hepatic resection is one of the most potentially curative treatments for HCC. Unfortunately, the long-term survival after radical hepatic resection is unsatisfactory because of the high incidence of tumor recurrence with the recurrence rates at 2 and 5 years are approximately 50 % to 60 % and 80 %,respectively. Microsatellite lesions, microvascular invasion (MVI) , or portal vein tumor thrombosis (PVTT) are the main risk factors for poor prognosis in HCC.
HCC is a typical vascular-rich tumor, and its occurrence, development, metastasis and invasion are closely related to angiogenesis. Due to the long-term chronic inflammatory response of the liver, the establishment and development of HCC can be induced by creating an immunosuppressive microenvironment, including up-regulation of PD-1 receptors. Therefore, immunotherapy is also considered to be a potential effective method for advanced HCC treatment. And there is little convincing evidence indicating that adjuvant therapy reduces the risk of recurrence after hepatic resection. Furthermore, no standard regimen has been established.
In the present study, we assessed the efficacy and safety of Apatinib Mesylate that is Small molecule anti-angiogenic targeted drugs /PD-1 antibody SHR-1210 combination therapy for surgically resected HCCs with high incidence of tumor recurrence containing microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Apatinib Mesylate +SHR-1210, Hepatic Arterial Infusion(HAI)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apatinib Mesylate +SHR-1210Combination product
Apatinib mesylate tablets: 250 mg, orally once a day. Take about half an hour after a meal with warm water (the daily dose should be as much as possible.
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. A total of 6 months of treatment,starting 4-8 weeks after radical hepatic resection.
Hepatic Arterial Infusion(HAI)Procedure or surgery
Twice standard HAI treatment, the first treatment was performed 4-8 weeks after radical hepatic resection, and the second treatment was given 4-8 weeks after the first treatment (the specific time interval depends on the recovery of liver function of the patient). The specific dosage regimen is 80-100 mg of epirubicin or 50 mg of epirubicin + oxaliplatin 50 mg per HAI treatment.
| Study group | Role | What they receive |
|---|---|---|
| Apatinib Mesylate +SHR-1210 | Experimental | Experimental arm: Apatinib mesylate +PD-1 antibody SHR-1210 for adjuvant therapy of HCC with high incidence of tumor recurrence after hepatic resection Receives: Combination Product: Apatinib Mesylate +SHR-1210 |
| Hepatic Arterial Infusion(HAI) | Active comparator | Active Comparator arm: HAI for adjuvant therapy of HCC with high incidence of tumor recurrence after hepatic resection Receives: Procedure: Hepatic Arterial Infusion(HAI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free survival(RFS)
Duration from surgery to tumor recurrence or death for any reason will be recorded to assess the clinical efficacy of Apatinib Mesylate plus PD-1 antibody SHR-1210 for HCC with high incidence of tumor recurrence after radical resection
Measured: 72 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start15 Feb 2019 (estimated)
- Primary completion28 Feb 2020 (estimated)
- Study completion28 Feb 2023 (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 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hong Zhao, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Hong Zhao, Study director, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03839550
- Sponsor's protocol ID
- CancerIHCAMS-HCC-SHR1210
- Status last verified
- Feb 2019
- First submitted
- 11 Feb 2019
- Last updated
- 15 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Multi-center, Randomized and Controlled Phase II Trail of Apatinib Mesylate Tablets Combined With PD-1 Antibody SHR-1210 for Adjuvant Treatment of Patients With High Recurrence Risk After Radical Operation of Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03839550
- Acronym / sponsor ID
- CancerIHCAMS-HCC-SHR1210
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 15 Feb 2019 (estimated)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 28 Feb 2023 (estimated)
- First posted
- 15 Feb 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 is to assess the efficacy and safety of Apatinib Mesylate combined with PD-1 antibody SHR-1210 in HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT) after radical resection. Patients will be randomized 1:1 either to the experimental arm to receive Apatinib Mesylate and PD-1 antibody SHR-1210 or to the standard therapy arm of hepatic arterial infusion(HAI) .
Detailed description
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, which is the third cause of cancer related deaths. Radical hepatic resection is one of the most potentially curative treatments for HCC. Unfortunately, the long-term survival after radical hepatic resection is unsatisfactory because of the high incidence of tumor recurrence with the recurrence rates at 2 and 5 years are approximately 50 % to 60 % and 80 %,respectively. Microsatellite lesions, microvascular invasion (MVI) , or portal vein tumor thrombosis (PVTT) are the main risk factors for poor prognosis in HCC.
HCC is a typical vascular-rich tumor, and its occurrence, development, metastasis and invasion are closely related to angiogenesis. Due to the long-term chronic inflammatory response of the liver, the establishment and development of HCC can be induced by creating an immunosuppressive microenvironment, including up-regulation of PD-1 receptors. Therefore, immunotherapy is also considered to be a potential effective method for advanced HCC treatment. And there is little convincing evidence indicating that adjuvant therapy reduces the risk of recurrence after hepatic resection. Furthermore, no standard regimen has been established.
In the present study, we assessed the efficacy and safety of Apatinib Mesylate that is Small molecule anti-angiogenic targeted drugs /PD-1 antibody SHR-1210 combination therapy for surgically resected HCCs with high incidence of tumor recurrence containing microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apatinib Mesylate +SHR-1210 | Experimental | Combination Product: Apatinib Mesylate +SHR-1210Experimental arm: Apatinib mesylate +PD-1 antibody SHR-1210 for adjuvant therapy of HCC with high incidence of tumor recurrence after hepatic resection |
| Hepatic Arterial Infusion(HAI) | Active comparator | Procedure: Hepatic Arterial Infusion(HAI)Active Comparator arm: HAI for adjuvant therapy of HCC with high incidence of tumor recurrence after hepatic resection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age between 18-75 years old.
- Patients were primary Hepatocellular carcinoma according to standardization of diagnosis and treatment for Hepatocellular carcinoma(2017 edition)
- The imaging examination confirmed complete response (CR) after 1 month radical surgery ,and consented to postoperative adjuvant therapy
- Preoperative imaging (CT/MRI/PET-CT), intraoperative or postoperative pathology confirmed HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invation(MVI) or secondary and above portal vein branches tumor thrombosis (PVTT) after radical resection.
- Preoperative imaging and perioperative outcomes confirmed no lymph node metastasis and distant metastasis.
Key exclusion criteria (23 listed)
- History of liver transplantation.
- Tumor rupture or invasion of adjacent organs.
- 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 .
- Subjects are allergic to Apatinib Mesylate Tablets, SHR-1210, pharmaceutical excipients, o 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 Mesylate +SHR-1210Apatinib mesylate tablets: 250 mg, orally once a day. Take about half an hour after a meal with warm water (the daily dose should be as much as possible. 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. A total of 6 months of treatment,starting 4-8 weeks after radical hepatic resection. | Combination product | Apatinib Mesylate +SHR-1210 |
| Hepatic Arterial Infusion(HAI)Twice standard HAI treatment, the first treatment was performed 4-8 weeks after radical hepatic resection, and the second treatment was given 4-8 weeks after the first treatment (the specific time interval depends on the recovery of liver function of the patient). The specific dosage regimen is 80-100 mg of epirubicin or 50 mg of epirubicin + oxaliplatin 50 mg per HAI treatment. | Procedure or surgery | Hepatic Arterial Infusion(HAI) |
Primary outcome
Recurrence-free survival(RFS)
Time frame: 72 month
Duration from surgery to tumor recurrence or death for any reason will be recorded to assess the clinical efficacy of Apatinib Mesylate plus PD-1 antibody SHR-1210 for HCC with high incidence of tumor recurrence after radical resection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
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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.
Hong Zhao study director
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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 +SHR-1210 and Hepatic Arterial Infusion(HAI) in people with Hepatocellular Carcinoma, 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 13 inclusion and 23 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 15 Feb 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 Hong Zhao (+86-13381106850, pumczhaohong@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-free survival(RFS) (time frame: 72 month). 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 15 Feb 2019.