The Safety and Efficacy of Thermal Ablation Combined With Apatinib and Carilimub for Advanced Liver Cancer

NCT04204577 | Unknown Phase 2

• 1 other identifier: S2019-128-02
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to two years

Secondary Outcomes (6)

• Objective response rate (ORR) according to RECIST 1.1

  Up to approximately two years

• Disease control rate(DCR)

  Up to approximately two years

• Overall survival(OS)

  Up to approximately two years

• Overall survival rate of 6 months and 12 months

  6 months and 12 months

• Safety: incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03

  Up to approximately two years

Study Arms (3)

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.

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.

Drug: Apatinib Mesylate

Interventions

Apatinib Mesylate DRUG

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.

Also known as: SHR-1210

Ablation combined with apatinib and PD-1 antibody SHR-1210; Thermal ablation combined with apatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Interventions

apatinib; camrelizumab

Study Officials

• Jie Yu

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Yu

CONTACT

8601066939530; yu-jie301@126.com

Xin Li

CONTACT

8601066937110

Study Design

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

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: December 19, 2019
• Study Start: November 1, 2019
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2023
• Last Updated: December 19, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)