Clinical trial NCT05613478: Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma
Official title: Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma: a Randomized, Open-label, Parallel, Multicenter Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Immunotherapy
Preoperative
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Jiangsu Hengrui Pharmaceutical Co., Ltd.
First posted: 2022-11-14
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 2 year event-free survival（2y-EFS）
timeFrame: 2-year
Secondary outcomes:
measure: R0 resection rate
timeFrame: 30-day
measure: The rate of subjects of major pathological response (MPR)
timeFrame: 30-day
measure: the rate of subjects with pathological complete response (pCR)
timeFrame: 30-day
measure: Overall survival (OS)
timeFrame: 3-year
measure: Event-free survival (EFS)
timeFrame: 3-year
measure: Disease-free survival (DFS)
timeFrame: 3-year
measure: Adverse event (AE)
timeFrame: 3-year
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Xuehao Wang, professor
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital with Nanjing Medical Univer
name: Yongxiang Xia
role: STUDY_DIRECTOR
References: