Ignite Creation Date:
2024-05-06 @ 6:07 PM
Last Modification Date:
2024-10-26 @ 2:42 PM
Study NCT ID:
NCT05550025
Status:
UNKNOWN
Last Update Posted:
2022-09-22
First Post:
2022-07-25
Brief Title:
TACE Combined With Camrelizumab and Apatinib in the Treatment of Advanced Liver Cancer
Sponsor:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Organization:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study Overview
Official Title:
A Single-center Prospective Single-arm Phase II Clinical Study on the Efficacy and Safety of TACE Combined With Camrelizumab and Apatinib in the Treatment of Advanced Liver Cancer
Status:
UNKNOWN
Status Verified Date:
2022-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study was designed to evaluate the effectiveness and safety of TACEtranscatheter arterial chemoembolization combined with Apatinib and Camrelizumab for Hepatocellular Carcinoma
The primary outcome measure is to evaluate the objective response rate ORR of the therapy for Hepatocellular Carcinoma
The secondary Outcome measures include the duration of response DOR disease control rate DCR progression-free survival rate PFSR Time Frame 6- and 12-month overall survival rate OSR Time Frame 6- and 12-month the median progression-free survival time mPFS and median overall survival time mOS of the therapy for Hepatocellular Carcinoma
Moreover this study aims to assess the safety and tolerability of the Therapy for Hepatocellular Carcinoma
The primary outcome measure is to evaluate the objective response rate ORR of the therapy for Hepatocellular Carcinoma
The secondary Outcome measures include the duration of response DOR disease control rate DCR progression-free survival rate PFSR Time Frame 6- and 12-month overall survival rate OSR Time Frame 6- and 12-month the median progression-free survival time mPFS and median overall survival time mOS of the therapy for Hepatocellular Carcinoma
Moreover this study aims to assess the safety and tolerability of the Therapy for Hepatocellular Carcinoma
Detailed Description:
Hepatocellular carcinoma is a common high-grade malignant tumor in my country with limited treatment options and poor prognosis Transcatheter arterial chemoembolization TACE is currently recognized as an effective method for the treatment of unresectable hepatocellular carcinoma Intra-arterial administration and embolization are the two major features of TACE treatment techniques However conventional TACE conventional TACE CTACE mainly focuses on the efficacy of embolization and the effect of chemotherapy is not ideal The emergence of drug-eluting beads DEB enhances the effect of chemotherapy in TACE which is of great significance to improve the overall efficacy of TACE in hepatocellular carcinoma However the long-term efficacy of TACE in the treatment of liver cancer is not very satisfactory Changes in the tumor microenvironment after TACE can induce abnormally elevated expression of tumor progression-related factors which makes liver cancer cells prone to local recurrence and distant metastasis which seriously affects the prognosis of liver cancer patients Clinical studies have shown that the complete tumor necrosis rate of TACE treatment of liver cancer is only 10-20 and the median survival time of patients is only 16-20 months Therefore the poor long-term efficacy of TACE is an urgent bottleneck for its application in the clinical treatment of liver cancer
With the deepening of tumor immune theory research based on overcoming the immune escape of swelling and pain the therapy that produces a specific and efficient immune response to swelling and pain has gradually become a hot spot in tumor research and great progress has been made Tumor immunotherapy has the advantages of high specificity remarkable curative effect and slight damage to normal organismsThe 2018 Nobel Prize in Physiology or Medicine was awarded to American scientist James R Alison and Japanese scientist Tasuku Honjo for their pioneering contributions to tumor immunotherapy With the in-depth study of the theory of swelling and pain immunology and the continuous progress of treatment technology it is expected to achieve a new breakthrough in the radical cure of swelling and pain and has gradually become the mainstream method of tumor treatment
Programmed death 1 PD-1programmed death-ligand 1 PD-L1 signaling pathway is currently the most mature and fastest-growing tumor immunotherapy molecule target PD-1 plays a role in the effector phase of the immune response and is expressed on activated T cells B cells and myeloid cells PD-1 has two ligands namely PD-L1 and PD-L2 Both PD-L1L2 are expressed in antigen-presenting cells and PD-L1 is also expressed in various tumor tissues The combination of PD-1 and PD-L1 mediates the co-inhibitory signal of T cell activation inhibits the killing function of T cells and negatively regulates the human immune response Therefore immunomodulation targeting PD-1PD-L1 is of great significance for anti-tumor therapy
Camrelizumab is a humanized PD-1 monoclonal antibody independently developed by Jiangsu Hengrui Medicine It has completed a phase clinical study for the treatment of solid pain The results show that camrelizumab has the potential to treat advanced solid pain Good safety and tolerability Objective response rate of camrelizumab in patients with previously treated advanced hepatocellular carcinoma A multi-center clinical trial of patients who received at least TACE Combination with camrelizumab and apatinib in the treatment of advanced liver tumors A single-center pre-fragile single-arm phase I clinical study Among patients receiving first-line systemic therapy the 6-month overall survival rate was 744 95CI680-797 with anti-swelling and pain activity and the safety was controllable so camrelizumab was approved for liver cancer indications on March 6 2020 for patients with advanced hepatocellular carcinoma who have previously received sorafenib andor oxaliplatin-containing 14795CI 103-202 systemic chemotherapy
Apatinib is a new-generation small-molecule vascular endothelial growth factor receptor-2 VEGFR-2 tyrosine kinase inhibitor and the worlds first small-molecule anti-angiogenic target proven safe and effective in the treatment of advanced gastric cancer Xiang drug independently developed by Jiangsu Hengrui Medicine its main mechanism of action is to highly selectively inhibit the signal transduction of VEGFR-2 combined with the micro-activity of succinic acid yang-blocking vascular endothelial growth factor VEGF thereby effectively inhibiting the Swelling angiogenesis In 2020 the randomized bilingual placebo-controlled phase W AHELP study of second-line apalachone in the treatment of late Ming hepatocellular brain CHCC jointly conducted by 31 tumor centers across the country was accepted by the ASCO General Assembly and selected as an oral presentation The results of the study showed that compared with placebo apatinib significantly prolonged median OS in previously treated Chinese patients with advanced HCC 87 months vs 68 months In addition the median progression-free survival PFS in the apatinib group was 45 months compared with 19 months in the placebo group at the same time the objective response rate ORR of the apatinib group was 107 which was significantly higher than that of the control group of 15 In terms of safety treatment-related adverse events were similar to those already approved for the treatment of late-stage gastric cancer no new adverse events were observed and patients were well tolerated Although apatinib has been submitted to the CFDA for second-line indications for hepatocellular carcinoma it has not yet been officially approved so it has not been written in the instructions that is it is an off-label drug
A phased study of apalacone combined with transarterial chemoembolization TACE in the treatment of advanced liver cancer was published in the journal Cancer Biology Therapy Preliminary conclusions showed that apazatinib combined with TACE treatment significantly improved ORR at 9 and 12 months and the median PFS was also significantly better than the control group 125 months vs 60 months Another single-center retrospective study also confirmed that the PFS and OS of apalacone combined with TACE in the treatment of advanced liver tumors were significantly better than those of the control group It can be seen that combined with apatinib treatment on the basis of TACE hopefully better Inhibit the growth of swelling disease to prolong the disease-free survival period and improve the survival rate of patients In 2018 a retrospective study was published at the World Congress on Pain and Pain Intervention WCIO suggesting the survival benefit of apalacone combined with TACE in the treatment of patients with HCC and portal vein tumor thrombus PVTT Apatinib combined with camrelizumab in the treatment of advanced liver cancer gastric cancer and esophagogastric junction cancer The phase clinical study also showed the synergistic effect of immunotherapy and anti-angiogenic therapy of which 16 cases of liver cancer can be evaluated for efficacy ORR and DCR were 50 and 938 respectively The results of the study were presented at the ASCO Annual meeting Apatinib in combination with camrelizumab for advanced liver cancer due to encouraging findings Phase clinical research is also actively carried out and all subjects have now been enrolled At the same time a single-center study on the efficacy and safety of apatinib combined with camrelizumab versus sorafenib in the first-line treatment of advanced hepatocyte TACE combined with camrelizumab and apatinib in the treatment of advanced liver cancer Prospective single-arm Phase II clinical trials of cancer cells in Sichuan have also been launched simultaneously in China the United States and Europe This randomized controlled open-label international multi-center study is the first exploration of the combination of PD-1 monoclonal antibody and anti-vascular targeting in my country in the field of liver cancer in the world We look forward to the announcement of the follow-up research results
With the deepening of tumor immune theory research based on overcoming the immune escape of swelling and pain the therapy that produces a specific and efficient immune response to swelling and pain has gradually become a hot spot in tumor research and great progress has been made Tumor immunotherapy has the advantages of high specificity remarkable curative effect and slight damage to normal organismsThe 2018 Nobel Prize in Physiology or Medicine was awarded to American scientist James R Alison and Japanese scientist Tasuku Honjo for their pioneering contributions to tumor immunotherapy With the in-depth study of the theory of swelling and pain immunology and the continuous progress of treatment technology it is expected to achieve a new breakthrough in the radical cure of swelling and pain and has gradually become the mainstream method of tumor treatment
Programmed death 1 PD-1programmed death-ligand 1 PD-L1 signaling pathway is currently the most mature and fastest-growing tumor immunotherapy molecule target PD-1 plays a role in the effector phase of the immune response and is expressed on activated T cells B cells and myeloid cells PD-1 has two ligands namely PD-L1 and PD-L2 Both PD-L1L2 are expressed in antigen-presenting cells and PD-L1 is also expressed in various tumor tissues The combination of PD-1 and PD-L1 mediates the co-inhibitory signal of T cell activation inhibits the killing function of T cells and negatively regulates the human immune response Therefore immunomodulation targeting PD-1PD-L1 is of great significance for anti-tumor therapy
Camrelizumab is a humanized PD-1 monoclonal antibody independently developed by Jiangsu Hengrui Medicine It has completed a phase clinical study for the treatment of solid pain The results show that camrelizumab has the potential to treat advanced solid pain Good safety and tolerability Objective response rate of camrelizumab in patients with previously treated advanced hepatocellular carcinoma A multi-center clinical trial of patients who received at least TACE Combination with camrelizumab and apatinib in the treatment of advanced liver tumors A single-center pre-fragile single-arm phase I clinical study Among patients receiving first-line systemic therapy the 6-month overall survival rate was 744 95CI680-797 with anti-swelling and pain activity and the safety was controllable so camrelizumab was approved for liver cancer indications on March 6 2020 for patients with advanced hepatocellular carcinoma who have previously received sorafenib andor oxaliplatin-containing 14795CI 103-202 systemic chemotherapy
Apatinib is a new-generation small-molecule vascular endothelial growth factor receptor-2 VEGFR-2 tyrosine kinase inhibitor and the worlds first small-molecule anti-angiogenic target proven safe and effective in the treatment of advanced gastric cancer Xiang drug independently developed by Jiangsu Hengrui Medicine its main mechanism of action is to highly selectively inhibit the signal transduction of VEGFR-2 combined with the micro-activity of succinic acid yang-blocking vascular endothelial growth factor VEGF thereby effectively inhibiting the Swelling angiogenesis In 2020 the randomized bilingual placebo-controlled phase W AHELP study of second-line apalachone in the treatment of late Ming hepatocellular brain CHCC jointly conducted by 31 tumor centers across the country was accepted by the ASCO General Assembly and selected as an oral presentation The results of the study showed that compared with placebo apatinib significantly prolonged median OS in previously treated Chinese patients with advanced HCC 87 months vs 68 months In addition the median progression-free survival PFS in the apatinib group was 45 months compared with 19 months in the placebo group at the same time the objective response rate ORR of the apatinib group was 107 which was significantly higher than that of the control group of 15 In terms of safety treatment-related adverse events were similar to those already approved for the treatment of late-stage gastric cancer no new adverse events were observed and patients were well tolerated Although apatinib has been submitted to the CFDA for second-line indications for hepatocellular carcinoma it has not yet been officially approved so it has not been written in the instructions that is it is an off-label drug
A phased study of apalacone combined with transarterial chemoembolization TACE in the treatment of advanced liver cancer was published in the journal Cancer Biology Therapy Preliminary conclusions showed that apazatinib combined with TACE treatment significantly improved ORR at 9 and 12 months and the median PFS was also significantly better than the control group 125 months vs 60 months Another single-center retrospective study also confirmed that the PFS and OS of apalacone combined with TACE in the treatment of advanced liver tumors were significantly better than those of the control group It can be seen that combined with apatinib treatment on the basis of TACE hopefully better Inhibit the growth of swelling disease to prolong the disease-free survival period and improve the survival rate of patients In 2018 a retrospective study was published at the World Congress on Pain and Pain Intervention WCIO suggesting the survival benefit of apalacone combined with TACE in the treatment of patients with HCC and portal vein tumor thrombus PVTT Apatinib combined with camrelizumab in the treatment of advanced liver cancer gastric cancer and esophagogastric junction cancer The phase clinical study also showed the synergistic effect of immunotherapy and anti-angiogenic therapy of which 16 cases of liver cancer can be evaluated for efficacy ORR and DCR were 50 and 938 respectively The results of the study were presented at the ASCO Annual meeting Apatinib in combination with camrelizumab for advanced liver cancer due to encouraging findings Phase clinical research is also actively carried out and all subjects have now been enrolled At the same time a single-center study on the efficacy and safety of apatinib combined with camrelizumab versus sorafenib in the first-line treatment of advanced hepatocyte TACE combined with camrelizumab and apatinib in the treatment of advanced liver cancer Prospective single-arm Phase II clinical trials of cancer cells in Sichuan have also been launched simultaneously in China the United States and Europe This randomized controlled open-label international multi-center study is the first exploration of the combination of PD-1 monoclonal antibody and anti-vascular targeting in my country in the field of liver cancer in the world We look forward to the announcement of the follow-up research results
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None