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出境医 / 临床实验 / SHR-1210 Plus Apatinib in Patients With Advanced-Stage Hepatocellular Carcinoma (SHR-1210)

SHR-1210 Plus Apatinib in Patients With Advanced-Stage Hepatocellular Carcinoma (SHR-1210)

Study Description
Brief Summary:
SHR-1210 is a humanized anti-PD-1 Immunoglobulin G4 (IgG4) monoclonal antibody. This is an open- label#single center #non-randomized #Single Arm Exploratory Study . This clinical study is an investigator-initiated clinical trial(IIT) .The objective of this study is to evaluate the efficacy and safety of therapy with anti-PD-1 antibody SHR-1210 and apatinib in patients with advanced stage hepatocellular carcinoma.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: SHR-1210 Drug: apatinib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm Pilot Study of Programmed Cell Death Protein 1 Antibody (PD-1# SHR-1210 Combined With Apatinib Mesylate in Patients With Advanced-Stage Hepatocellular Carcinoma
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : October 1, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: SHR-1210+ apatinib
SHR-1210 was administered intravenously (without prophylaxis) at a fixed dose of 200 mg for 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 2 years; Apatinib was taken orally after meals, once a day, for continuous medication, and 1 cycle every 4 weeks.
Drug: SHR-1210
SHR-1210 is a humanized anti-PD-1 IgG4 monoclonal antibody
Other Name: Anti-PD-1 Antibody

Drug: apatinib
Apatinib is a selective VEGFR2 inhibitor.

Outcome Measures
Primary Outcome Measures :
  1. Objective response rate(ORR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard


Secondary Outcome Measures :
  1. Progression free survival(PFS) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard

  2. To the relief time (TOR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard

  3. Duration of relief(DOR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard

  4. Disease Control Rate (DCR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard

  5. 9-month survival rate [ Time Frame: 9-month ]
  6. 12-month survival rate [ Time Frame: 12-month ]
  7. Overall survival (OS) [ Time Frame: 10 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1.≥18 years old, male or female 2.Advanced liver cancer (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C 3.Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 4.Patient has given written informed consent. 5.Previous treatment failure with sorafenib or rivastatin (disease of disease or toxicity) or unwillingness to accept, economically unsustainable sorafenib treatment; 6.The function of important organs meets the requirements 7.Expected survival ≥12 weeks 8.Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period; non-surgical sterilization Female patients of childbearing age must have a negative serum or urine human chorionic gonadotropin(HCG) test within 72 hours prior to study enrollment; and must be non-lactating; for male patients with maternal age, they should be given SHR-1210 during the trial and after the last 3 effective methods of contraception within a month.

Exclusion Criteria:

- 1.The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included); 2.The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment; 3.Have clinical symptoms or disease that are not well controlled 4.Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization 5.Arterial/venous thrombosis in the first 6 months of randomization 6.According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.,with family or social factors, it will affect the safety of patients.

7.Liver tumor burden greater than 50% of the total liver volume, or patients who have previously undergone liver transplantation;Known for a history of central nervous system metastasis or hepatic encephalopathy;Severe allergic reactions to other monoclonal antibodies;

Contacts and Locations

Contacts
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Contact: Jia Fan, PHD 021 64041990/680774 :fan.jia@zs-hospital.sh.cn

Locations
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China, Shanghai
Zhongshan Hospital Recruiting
Shanghai, Shanghai, China, 200032
Contact: : Jia Fan, PHD    021 64041990/680774    fan.jia@zs-hospital.sh.cn   
Sponsors and Collaborators
Shanghai Zhongshan Hospital
Tracking Information
First Submitted Date  ICMJE July 8, 2019
First Posted Date  ICMJE July 10, 2019
Last Update Posted Date July 11, 2019
Actual Study Start Date  ICMJE June 1, 2019
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
Objective response rate(ORR) [ Time Frame: 2 years ]
Evaluated by researchers based on the RECIST 1.1 standard
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
  • Progression free survival(PFS) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard
  • To the relief time (TOR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard
  • Duration of relief(DOR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard
  • Disease Control Rate (DCR) [ Time Frame: 2 years ]
    Evaluated by researchers based on the RECIST 1.1 standard
  • 9-month survival rate [ Time Frame: 9-month ]
  • 12-month survival rate [ Time Frame: 12-month ]
  • Overall survival (OS) [ Time Frame: 10 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SHR-1210 Plus Apatinib in Patients With Advanced-Stage Hepatocellular Carcinoma
Official Title  ICMJE A Single Arm Pilot Study of Programmed Cell Death Protein 1 Antibody (PD-1# SHR-1210 Combined With Apatinib Mesylate in Patients With Advanced-Stage Hepatocellular Carcinoma
Brief Summary SHR-1210 is a humanized anti-PD-1 Immunoglobulin G4 (IgG4) monoclonal antibody. This is an open- label#single center #non-randomized #Single Arm Exploratory Study . This clinical study is an investigator-initiated clinical trial(IIT) .The objective of this study is to evaluate the efficacy and safety of therapy with anti-PD-1 antibody SHR-1210 and apatinib in patients with advanced stage hepatocellular carcinoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: SHR-1210
    SHR-1210 is a humanized anti-PD-1 IgG4 monoclonal antibody
    Other Name: Anti-PD-1 Antibody
  • Drug: apatinib
    Apatinib is a selective VEGFR2 inhibitor.
Study Arms  ICMJE Experimental: SHR-1210+ apatinib
SHR-1210 was administered intravenously (without prophylaxis) at a fixed dose of 200 mg for 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 2 years; Apatinib was taken orally after meals, once a day, for continuous medication, and 1 cycle every 4 weeks.
Interventions:
  • Drug: SHR-1210
  • Drug: apatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2020
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1.≥18 years old, male or female 2.Advanced liver cancer (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C 3.Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 4.Patient has given written informed consent. 5.Previous treatment failure with sorafenib or rivastatin (disease of disease or toxicity) or unwillingness to accept, economically unsustainable sorafenib treatment; 6.The function of important organs meets the requirements 7.Expected survival ≥12 weeks 8.Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period; non-surgical sterilization Female patients of childbearing age must have a negative serum or urine human chorionic gonadotropin(HCG) test within 72 hours prior to study enrollment; and must be non-lactating; for male patients with maternal age, they should be given SHR-1210 during the trial and after the last 3 effective methods of contraception within a month.

Exclusion Criteria:

- 1.The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included); 2.The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment; 3.Have clinical symptoms or disease that are not well controlled 4.Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization 5.Arterial/venous thrombosis in the first 6 months of randomization 6.According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.,with family or social factors, it will affect the safety of patients.

7.Liver tumor burden greater than 50% of the total liver volume, or patients who have previously undergone liver transplantation;Known for a history of central nervous system metastasis or hepatic encephalopathy;Severe allergic reactions to other monoclonal antibodies;

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jia Fan, PHD 021 64041990/680774 :fan.jia@zs-hospital.sh.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04014101
Other Study ID Numbers  ICMJE ZSGW-PD-1210
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Shanghai Zhongshan Hospital
Study Sponsor  ICMJE Shanghai Zhongshan Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Shanghai Zhongshan Hospital
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP