Camrelizumab Combined With Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma

Phase 2

Active, not recruiting

• Conditions: Molecular Targeted Therapy; Hepatocellular Carcinoma; Immunotherapy
• Interventions: Drug: Camrelizumab; Drug: Apatinib Mesylate; Procedure: Radical surgery

• Registration Number: NCT04521153
• Lead Sponsor: Shanghai Zhongshan Hospital

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 the rate of subjects with major pathological response for phase 2 study and event-free survival (EFS) by investigator for phase 3 study of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate EFS by Blinded Independent Review Committee, the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, overall survival and disease-free 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 (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. One cycle of postoperative TACE treatment is allowed in both experimental and control group. The primary purpose of this study is to evaluate the rate of subjects with major pathological response for phase 2 study and event-free survival (EFS) by investigator for phase 3 study of camrelizumab combined with apatinib mesylate in the perioperative period of HCC. The secondary research purpose is to evaluate the EFS by Blinded Independent Review Committee, the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, overall survival and disease-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable HCC. The safety and tolerability is also evaluated.

Study Timeline

• Study First Submitted: 2020-08-18
• Study First Submitted QC: 2020-08-19
• Study First Posted: 2020-08-20
• Study Start: 2021-03-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2025-07-31
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 294

Inclusion Criteria

1. Volunteer to participate in this study and sign an informed consent form
2. Age 18~75 years old, no gender limit
3. Hepatocellular carcinoma confirmed by histopathology, cytology or imaging
4. CNLC stage Ib/IIa/IIb/IIIa hepatocellular carcinoma, except for CNLC IIIa hepatocellular carcinoma combined with main portal vein tumor thrombus
5. Child-Pugh score: A grade (≤6 points)
6. ECOG PS score: 0-1 points

Exclusion Criteria

1. 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.
2. Currently accompanied by interstitial pneumonia or interstitial lung disease
3. Existence of active autoimmune disease or history of autoimmune disease and may relapse
4. Patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or baseline white blood cell count >15*10^9/L
5. Patients with congenital or acquired immune deficiencies (such as HIV-infected persons)
6. Those who are known to be allergic to any monoclonal antibodies, anti-angiogenesis targeted drugs or excipients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Camrelizumab	Preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery →sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles). One cycle of postoperative TACE treatment 4-6 weeks after surgery is allowed. (Note: Surgery within 2-4 weeks after the last administration of neoadjuvant therapy, postoperative TACE treatment at least 4 weeks after surgery, and camrelizumab combined with apatinib mesylate 4 weeks after surgery or 2-4 weeks after post-operative TACE)
Experimental group	Apatinib Mesylate	Preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery →sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles). One cycle of postoperative TACE treatment 4-6 weeks after surgery is allowed. (Note: Surgery within 2-4 weeks after the last administration of neoadjuvant therapy, postoperative TACE treatment at least 4 weeks after surgery, and camrelizumab combined with apatinib mesylate 4 weeks after surgery or 2-4 weeks after post-operative TACE)
Experimental group	Radical surgery	Preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery →sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles). One cycle of postoperative TACE treatment 4-6 weeks after surgery is allowed. (Note: Surgery within 2-4 weeks after the last administration of neoadjuvant therapy, postoperative TACE treatment at least 4 weeks after surgery, and camrelizumab combined with apatinib mesylate 4 weeks after surgery or 2-4 weeks after post-operative TACE)
Control group	Radical surgery	Radical surgery, one cycle of postoperative TACE treatment 4-6 weeks after surgery is allowed. (Note: Postoperative TACE treatment at least 4 weeks after surgery)

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS) assessed by investigator	up to 3 years	The primary endpoint of phase 3 study is EFS assessed by investigator, which 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.
The rate of subjects of major pathological response (MPR)	From enrollment to 30 days post-surgery	The primary endpoint of phase 2 study is the rate of subjects of MPR in the first 60 patients in the experimental group. MPR is defined as less than or equal to 50% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy.

Secondary Outcome Measures

Name	Time	Method
Disease-free survival (DFS) assessed by investigator	up to 3 years	DFS is defined as the time from randomization until disease recurrence or death from any cause.
R0 resection rate	From enrollment to 30 days post-surgery	R0 resection rate
The rate of subjects of pathologic complete response (pCR)	From enrollment to 30 days post-surgery	The rate of subjects of pCR
Safety and tolerability	From enrollment to the end of treatment at 90 days	The incidence of adverse events, severe adverse events; surgery related safety.
Overall survival (OS)	up to 5 years	OS is defined as the time from randomisation to death.
EFS assessed by Blinded Independent Review Committee (BIRC)	up to 3 years	The primary endpoint of phase 3 study is EFS assessed by BIRC, which was retrospectively reviewed by two independent radiologists. 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.
The rate of subjects of major pathological response (MPR)	From enrollment to 30 days post-surgery	The rate of subjects of MPR in all enrolled patients. MPR is defined as less than or equal to 50% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy.

Trial Locations

Locations (1)

180 Fenglin Road; 🇨🇳 Shanghai, Shanghai, China