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

Fudan University

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Molecular Targeted Therapy; Immunotherapy; Hepatocellular Carcinoma

Treatments: Procedure: Radical surgery; Drug: Apatinib Mesylate; Drug: Camrelizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04521153

ZS-ZJ-SK-2020

Details and patient eligibility

About

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.

Full 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.

Enrollment: 294 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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294 participants in 2 patient groups

Experimental group

Experimental group

Description:

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)

Treatment:

Drug: Camrelizumab

Drug: Apatinib Mesylate

Procedure: Radical surgery

Control group

Active Comparator group

Description:

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)

Treatment:

Procedure: Radical surgery