TACE Combined With Sintilimab Plus Bevacizumab Biosimilar in Hepatocellular Carcinoma (BCLC-C Stage ): a Prospective Single-arm Phase II Clinical Study

NCT04796025 | Unknown Phase 2

• 1 other identifier: T-Double
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with pd-1 antibody immunotherapy (Sintilimab) and anti-VEGF (Bevacizumab Biosimilar) in patients with advanced hepatocellular carcinoma (BCLC-C Stage).

Conditions

Hepatocellular Carcinoma

Keywords

TACE; Sintilimab; Bevacizumab Biosimilar; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1 and mRECIST

  ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)

Secondary Outcomes (6)

• Disease control rate (DCR)

  From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)

• Duration of response (DOR) by RECIST 1.1 and mRECIST

  From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to 2 years)

• Progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST

  From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to 2 years)

• Overall survival rate (OSR)

  From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)

• Progression-free survival time (mPFS)

  From date of first dose of study drug to the date of first documentation of disease progression (up to 2 years)

Other Outcomes (1)

• Treatment-related adverse events

  From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

Study Arms (1)

T-Double

EXPERIMENTAL

TACE Combined With Sintilimab Plus Bevacizumab Biosimilar

Drug: Sintilimab; Bevacizumab Biosimilar

Interventions

Sintilimab; Bevacizumab Biosimilar DRUG

1-4 cycles, intra-arterial infusion: sindilimab 200mg + bevacizumab 7.5mg/kg, q3w; 5-18 cycles: Sintilimab (200mg ivdrip D1 Q3W)+Bevacizumab Biosimilar (15mg/kg ivdrip D1 Q3W）

Also known as: TACE

T-Double

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient voluntarily joined the study and signed an informed consent form;
• ≥18 and ≤69 years old, both male and female;
• Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma (unresectable or metastatic), at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm);
• Child-Pugh score ≤ 6 points (Child-Pugh A);
• BCLC staging is stage C; PVTT classification is combined with PVTT (program classification PVTT ≤ 3), and a single lesion in the liver (or multiple lesions with diameter) ≤ 7cm of primary liver cancer.
• Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past;
• ECOG score: 0～1 (see Annex 1 for ECOG scoring criteria);
• Expected survival period ≥ 12 weeks;
• The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration):
• The absolute count of neutrophils≥1.5×109/L; Platelet ≥80×109/L; Hemoglobin ≥90 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤1.5×ULN (within 7 days before the first administration); ALT and AST ≤3×ULN (within 7 days before the first dose); AKP≤ 2.5×ULN; Serum creatinine≤1.5×ULN;
• Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, Carelil should be given during the trial and at the last time Use effective methods for contraception within 3 months after the onslumab.

You may not qualify if:

• The patient has any active autoimmune disease or a history of autoimmune disease;
• The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose\>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
• The number of system treatment lines ≥ 2 lines;
• Severe allergic reaction to other monoclonal antibodies;
• Those with a known history of central nervous system metastasis or hepatic encephalopathy;
• Patients whose liver tumor burden is greater than 50% of the total liver volume, or who have received liver transplantation in the past;
• Ascites with clinical symptoms, those who need puncture, drainage, or those who have received ascites drainage within the past 3 months, except those who have only a small amount of ascites on imaging but not accompanied by clinical symptoms;
• Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc\>450ms (male); QTc\>470ms (female);
• Abnormal coagulation function (INR\>2.0, PT\>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
• Significant clinically significant bleeding symptoms or clear bleeding tendency occurred within 3 months before randomization, such as pertussis/hemoptysis 2.5ml or more, gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic stomach Ulcer or vasculitis, etc., if the stool occult blood is positive at the baseline, it can be re-examined. If it is still positive after the re-examination, a gastroscopy is required. If the gastroscope shows severe esophageal and gastric varices, it cannot be included in the group (3 before the group) Except those who have undergone gastroscopy within a month or less to exclude such cases);
• Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content\> 1.0 g;
• Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication \<5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1;
• The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count \>15×109/L; Patients with congenital or acquired immune deficiencies (such as HIV-infected persons);

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab

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

Central Study Contacts

Fei Gao, M.D.

CONTACT

86-13760869828; gaof@sysucc.org.cn

Zhenkang Qiu, M.D.

CONTACT

86-18811845585; qiuzk@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 12, 2021
• Study Start: September 23, 2021
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2024
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)