Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
At the time of diagnosis, the majority of hepatocellular carcinoma (HCC) patients are at the intermediate to advanced stages, with a 50-70% incidence of macrovascular invasion (including portal vein, hepatic vein, inferior vena cava, or bile duct invasion). Tyrosine kinase inhibitors (TKI, including lenvatinib and sorafenib) or a combination of TKIs and immune therapy is one of the standard treatment options recommended by HCC guidelines. However, numerous retrospective studies have reported that for surgically resectable HCC with macrovascular invasion, surgical resection yields better efficacy than non-surgical treatments (including transarterial interventional therapies and/or systemic therapies). Nevertheless, the postoperative recurrence rate remains exceedingly high, exceeding 80%. Therefore, determining comprehensive approaches to enhance surgical radicality and reduce postoperative recurrence rates is a current research hotspot.
Recent studies have found that neoadjuvant therapy (including immunotherapy alone or in combination with TKI) before surgery can reduce postoperative recurrence rates and extend survival rates. Moreover, SBRT combined with TKI and immunotherapy has a sensitizing effect, particularly showing good sensitivity and control rates for vascular invasion.
Thus, this study aims to conduct a prospective, single-arm phase II clinical trial targeting patients with surgically resectable HCC with macrovascular invasion. The primary endpoints are objective response rate (ORR) and treatment completion rate, to evaluate the efficacy and safety of the preoperative neoadjuvant therapy with the combination of SBRT, lenvatinib, and pucotenlimab (an anti PD-1 drug). The secondary endpoints include progression-free survival (PFS), overall survival (OS), incidence of adverse events, pathological response rate, and incidence of surgical complications, to preliminarily evaluate the efficacy of the neoadjuvant therapy with this triple regimen.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental arm | Experimental | After enrollment, patients will immediately begin treatment with Lenvatinib (Len) and Pucotenlimab (Puco). SBRT will be performed within 2-4 weeks after enrollment (with continued Len plus Puco during this period). Six to ten weeks after the completion of SBRT, imaging assessments will be conducted. If there is no sign of tumor progression (PD), surgical resection will be performed within 10-16 weeks after the completion of SBRT. A total of four cycles of Puco treatment must be completed before surgery. The surgical resection should conducted within two weeks after completing the fourth cycle of Puco. Len should be discontinued one week before surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neoadjuvant SBRT combined with Lenvatinib and Pucotenlimab | Drug | SBRT: SBRT will be performed within 2-4 weeks after enrollment. The total radiation dose will be 24 Gy, delivered in 3 fractions on alternate days, to be completed within one week. Lenvatinib: 8mg/day, begin immediately after enrollment. Lenvatinib should be discontinued one week before surgery. Pucotenlimab: 200mg，3-week interval between cycles, begin immediately after enrollment, a total of four cycles of Puco treatment must be completed before surgery. Surgical resection will be performed within 10-16 weeks after the completion of SBRT. |
| Measure | Description | Time Frame |
|---|---|---|
| objective response rate (ORR) | The ratio of patients achieving the best efficacy of neoadjuvant therapy, including complete response (CR) and partial response (PR), to all patients. | From date of neoadjuvant treatment beginning until the date of neoadjuvant treatment completion, up to 1 year. |
| treatment complete rate (TCR) | The ratio of patients completing the neoadjuvant therapy to all patients. | From date of neoadjuvant treatment beginning until the date of neoadjuvant treatment completion, up to 1 year. |
| Measure | Description | Time Frame |
|---|---|---|
| progression-free survival (PFS) | PFS is defined as the time from treatment to the first confirmed disease progression. For patients who undergo surgical resection, disease progression is defined as postoperative recurrence/metastasis. For patients who do not undergo surgical resection, disease progression is confirmed based on imaging assessment according to the mRECIST criteria. | From date of neoadjuvant treatment beginning until the date of follow-up completion, up to 2 year. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Yaojun Zhang | Sun Yat-sen University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | 510060 | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| overall survival (OS) | OS is defined as the time from randomization to death from any cause | From date of neoadjuvant treatment beginning until the date of death from any cause, assessed up to 2 years. |
| incidence of adverse events (safety ) | Treatment-related adverse events are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0). | From date of neoadjuvant treatment beginning until 3 months after treatment completion, up to 1 year. |
| perioperative complication rate | Perioperative complication includes intraoperative complications such as bleeding and transfusion, extensive adhesions, diaphragm resection, prolonged surgery time, etc., as well as postoperative complications such as bleeding, infection, bile leakage, liver dysfunction, etc. | The period from the start of surgery to the patient's discharge from hospital, up to 1 year. |
| pathological complete response (pCR) | The ratio of patients with no viable tumor cells in the pathology after resection to all patients undergoing surgical resection. | From date of neoadjuvant treatment beginning until the date of surgical resection completion, up to 1 year. |
| ID | Term |
|---|---|
| C531958 | lenvatinib |
Not provided
Not provided
Not provided