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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental group | Experimental | 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 | Active Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Camrelizumab | Drug | Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival (EFS) assessed by investigator | 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. | up to 3 years |
| The rate of subjects of major pathological response (MPR) | 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. | From enrollment to 30 days post-surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | OS is defined as the time from randomisation to death. | up to 5 years |
| EFS assessed by Blinded Independent Review Committee (BIRC) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jian Zhou, Doctor | Shanghai Zhongshan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 180 Fenglin Road | Shanghai | Shanghai Municipality | 200032 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
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| Apatinib Mesylate | Drug | Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery |
|
| Radical surgery | Procedure | Radical surgery |
|
| up to 3 years |
| Disease-free survival (DFS) assessed by investigator | DFS is defined as the time from randomization until disease recurrence or death from any cause. | up to 3 years |
| R0 resection rate | R0 resection rate | From enrollment to 30 days post-surgery |
| The rate of subjects of major pathological response (MPR) | 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. | From enrollment to 30 days post-surgery |
| The rate of subjects of pathologic complete response (pCR) | The rate of subjects of pCR | From enrollment to 30 days post-surgery |
| Safety and tolerability | The incidence of adverse events, severe adverse events; surgery related safety. | From enrollment to the end of treatment at 90 days |
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| 41125112 | Derived | Wang Z, Fan J, Zhou S, Sun Y, Liang F, Ji Y, Gu F, Li T, Peng L, Peng T, Huang X, Ding Z, Bai D, Xiang B, Tan G, Wen T, Zeng Y, Han F, Zhang Y, Wu S, Zhao H, Chen Y, Shi G, Hou Z, Sun Y, Zhu W, Zhou J. Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial. Lancet. 2025 Nov 1;406(10515):2089-2099. doi: 10.1016/S0140-6736(25)01720-9. Epub 2025 Oct 19. |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| C000631724 | camrelizumab |
| C553458 | apatinib |
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