Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma: a Randomized, Open-label, Parallel, Multicenter Trial
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- 2 year event-free survival（2y-EFS）
Overview
Brief Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The primary purpose of this study is to evaluate 2 year event-free survival（2y-EFS） of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.
Detailed Description
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. This trial includes subjects with CNLC Ib/IIa/IIb/IIIa HCC. All eligible subjects will be randomized (1:1) to experimental group or control group. In the experimental group, patients will be treated with following: neoadjuvant therapy ( perioperative TACE treatment，camrelizumab and apatinib, 2 cycles), radical surgery, adjuvant therapy (camrelizumab and apatinib, 6 cycles); in the control group, patients will be treated with following: radical surgery,adjuvant therapy (camrelizumab and apatinib, 6 cycles). The primary purpose of this study is to evaluate 2 year event-free survival（2y-EFS） of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Volunteer to participate in this study and sign an informed consent form.
- •Age ≥18 years old, no gender limit.
- •Hepatocellular carcinoma confirmed by histopathology, cytology or imaging.
- •CNLC stage Ib (single tumor with diameter ≥8 cm)/IIa/IIb/IIIa hepatocellular carcinoma, except for CNLC IIIa hepatocellular carcinoma combined with main portal vein tumor thrombus；multiple hepatocellular carcinoma was allowed to be treated with surgical excision combined with intraoperative ablation.
- •Child-Pugh score: A grade (≤6 points).
- •ECOG PS score: 0-1 points.
Exclusion Criteria
- •Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; have other active malignancies other than HCC within 5 years or at the same time.
- •Currently accompanied by interstitial pneumonia or interstitial lung disease.
- •Existence of active autoimmune disease or history of autoimmune disease and may relapse.
- •Patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or baseline white blood cell count \>15\*10\^9/L.
- •Patients with congenital or acquired immune deficiencies (such as HIV-infected persons).
- •Those who are known to be allergic to any monoclonal antibodies, anti-angiogenesis targeted drugs or excipients.
Arms & Interventions
Experimental group
Preoperative TACE treatment → preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Camrelizumab (Drug)
Experimental group
Preoperative TACE treatment → preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Apatinib Mesylate (Drug)
Experimental group
Preoperative TACE treatment → preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Radical surgery (Procedure)
Experimental group
Preoperative TACE treatment → preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Preoperative TACE treatment (Procedure)
Control group
Radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Radical surgery (Procedure)
Control group
Radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Camrelizumab (Drug)
Control group
Radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)
Intervention: Apatinib Mesylate (Drug)
Outcomes
Primary Outcomes
2 year event-free survival（2y-EFS）
Time Frame: 2-year
2y-EFS is defined as time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.
Secondary Outcomes
- R0 resection rate(30-day)
- The rate of subjects of major pathological response (MPR)(30-day)
- the rate of subjects with pathological complete response (pCR)(30-day)
- Overall survival (OS)(3-year)
- Event-free survival (EFS)(3-year)
- Disease-free survival (DFS)(3-year)
- Adverse event (AE)(3-year)
Investigators
Xuehao Wang
professor
The First Affiliated Hospital with Nanjing Medical University