Combine Apatinib Mesylate With PD-1 Antibody SHR-1210 for HCC With High Risk of Recurrence After Radical Resection

NCT03839550 | Unknown Phase 2 DMC

• 1 other identifier: CancerIHCAMS-HCC-SHR1210
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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) .

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  72 month

Study Arms (2)

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

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

Procedure: Hepatic Arterial Infusion(HAI)

Interventions

Apatinib Mesylate +SHR-1210 COMBINATION_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.

Apatinib Mesylate +SHR-1210

Hepatic Arterial Infusion(HAI) PROCEDURE

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.

Hepatic Arterial Infusion(HAI)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Hong Zhao

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Hong Zhao

CONTACT

+86-13381106850; pumczhaohong@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: February 15, 2019
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2023
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

CN (1)