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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: SHR-1210; Drug: apatinib

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jia Fan, PHD; Phone Number: 021 64041990/680774; Email: :fan.jia@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital
      • Contact: : Jia Fan, PHD; Phone Number: 021 64041990/680774; Email: fan.jia@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Anti-PD-1 Antibody; Drug: apatinib; Apatinib is a selective VEGFR2 inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To the relief time (TOR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Duration of relief(DOR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Disease Control Rate (DCR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Progression free survival(PFS)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
9-month survival rate		9-month
12-month survival rate		12-month
Overall survival (OS)		10 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (ACTUAL): July 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: ZSGW-PD-1210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No