Hepatocellular Carcinoma, Immunotherapy, Molecular Targeted Therapy
Conditions
Keywords
Camrelizumab; apatinib mesylate; hepatocellular carcinoma
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.
Interventions
DRUGCamrelizumab
Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery
DRUGApatinib Mesylate
Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery
PROCEDURERadical surgery
Radical surgery
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall survival (OS) | up to 5 years | OS is defined as the time from randomisation to death. |
| 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. |
| 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. |
| 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. |
Countries
China
Outcome results
None listed