Sun Yat-sen University Cancer Center
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab; Bevacizumab Biosimilar
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR) by RECIST 1.1 and mRECIST
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
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).
Detailed Description
This is a prospective, single arm, phase II study to evaluate the efficacy and safety of TACE combined with Sintilimab and Bevacizumab Biosimilar (T-Double Therapy) in patients with HCC (BCLC-C Stage). Subjects who meet the admission criteria will be treated with Sintilimab and Bevacizumab Biosimilar after TACE until disease progression, intolerable toxicity, death, withdrawal of the patient or the researchers determined that the drug must be discontinued. The primary outcome measure is to evaluate the objective response rate (ORR) of T-Double Therapy for advanced HCC (BCLC C-stage). The secondary outcome measures include the duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) in 6- and 12-months, overall survival rate (OSR) in 6- and 12-months, the median progression-free survival time (mPFS) and median overall survival time (mOS) of T-Double Therapy for advanced HCC. This study also aims to assess the safety and adverse reactions of T-Double Therapy for advanced HCC.
Investigators
Fei Gao
Chief physician
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
T-Double
TACE Combined With Sintilimab Plus Bevacizumab Biosimilar
Intervention: Sintilimab; Bevacizumab Biosimilar
Outcomes
Primary Outcomes
Objective response rate (ORR) by RECIST 1.1 and mRECIST
Time Frame: 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)
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
Secondary Outcomes
- 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))
- 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))
- Median overall survival time (mOS)(From the start date of the Treatment Phase until date of death from any cause (up to 2 years))