Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06590844
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
None
First Post:
2024-03-04
Brief Title:
cindilizumab Bevacizumab Coenzyme I for Injection in Unresectable Hepatocellular Carcinoma
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Exploratory Study on the Efficacy and Safety of cindilizumab Bevacizumab Coenzyme I for Injection in Unresectable Hepatocellular Carcinoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is a single-arm single-center non-randomized open-label study A total of 37 patients with locally advanced or metastatic HCC who have not received systemic therapy are not suitable for radical surgical resection or local treatment or have disease progression after surgical resection or local treatment the efficacy and safety of cindilizumab bevacizumab coenzyme I for injection are initially explored
Detailed Description:
1 Background According to the latest global cancer burden data for 2020 released by the World Health Organization Agency for International Research on Cancer IARC about 390000 people die from liver cancer every year accounting for 47 percent of the global liver cancer deaths As the second mortality malignant tumor in China the five-year survival rate is only 14 Based on the ORIENT-32 study the first PD-1 immunosuppressive combination therapy sindilizumab combined with bevacizumab for the first-line treatment of patients with advanced liver cancer has been officially approved by the National Drug Administration for the first-line treatment of unresectable or metastatic liver cancerSindilizumab bevacizumab marks a breakthrough in liver cancer immunotherapy with the combination of PD-1 immunosuppressive agents However clinical trial data showed that the response rate of immunosuppressive agents in solid tumors was low ORIENT-32 ORR of Sindilizumab bevacizumab regimen was 25 and susceptible to tolerance Therefore finding effective efficacy predictive markers and combination therapy is an important method to improve the effect of tumor immunotherapy and promote tumor precision immunotherapy
Coenzyme I nicotinamide adenine dinucleotide NAD Is a very important coenzyme in biological redox reactions and plays a crucial role in various biological processes including metabolism senescence cell death DNA repair and gene expressionNADMetabolic abnormalities are closely related to the occurrence and development of many diseases including cancer On November 92020 Academician Wang Hongyangs team published the title NAD on Cell Metabolismmetabolism maintains inducible PD-L1 expression to drive tumor immune evasion research paper reveals the NADMetabolism drives novel mechanisms of tumor immune escape by regulating immune checkpoint PD-L1 expression and is proposed by supplementing NADNovel strategies to enhance therapeutic sensitivity of anti-PD-1 PD-L1 antibodies5 Further studies found that the anti-PD-1 antibody suppressed tumor burden by 422 in a model of Hep 1-6-CD38 immunotherapy administered NADThe tumor burden suppression rate after the combination therapy was 828 In the primary tolerance model of Pan02 immunotherapy in pancreatic cancer the anti-PD-1 antibody suppressed tumor burden by only 186 giving NADThe combined treatment tumor burden suppression rate was 647 In both models simultaneously the NADThe group alone did not promote tumor growth compared with the control group The study has important clinical implications to complement the NADA combination regimen with anti-PD-1 PD-L1 antibodies could provide a novel therapeutic strategy for tumors resistant to immunotherapy
2Effectiveness evaluation indicators primary efficacy indicators and secondary efficacy indicators Primary endpoint
ORR as assessed by mRECIST 11 Selected secondary study endpoints and exploratory endpoints
Safety and tolerability
DOR DCR PFS TTP OS as assessed by mRECIST 11
Conversion rate Safety evaluation index The incidence and severity of all adverse events AEs treatment emergent adverse events TEAEs grade 3 or higher study drug-related adverse events serious adverse events SAEs were judged according to CTCAE V50 and the clinical characteristics severity time of occurrence of any adverse events were recorded End time duration treatment measures and outcomes and determine their relevance to treatment regimens
3Statistical Methods All statistical analyses will be performed in SAS 94 or later In general continuous variables will be statistically described using the number of cases mean median standard deviation minimum and maximum values Categorical and hierarchical variables will be statistically described using the frequency and percentage of each category or grade and missing values will not be included in the calculation of percentages unless otherwise indicated Unless otherwise stated all statistical tests will be performed using a two-sided test of α 005 with a two-sided 95 confidence interval CI calculated
4Statistical processing All statistical analyses will be performed using SAS 94 or later In general continuous variables will be statistically described using the number of cases mean median standard deviation minimum and maximum values Categorical and hierarchical variables will be statistically described using the frequency and percentage of each category or grade and missing values will not be included in the calculation of percentages unless otherwise indicated Unless otherwise stated all statistical tests will be performed using a two-sided test of α 005 with a two-sided 95 confidence interval CI calculated
5Data security monitoring The clinical study will develop a data security monitoring plan according to the size of the risk All adverse events are recorded in detail properly handled and tracked until properly resolved or the condition is stable and serious adverse events and unexpected events are reported to the ethics committee competent authorities and drug regulatory departments in a timely manner in accordance with regulations The principal investigator conducted a systematic review of all adverse events on a regular basis and convened investigator meetings to assess the risks and benefits of the study if necessary Double-blind trials can be urgently unblinded if necessary to ensure the safety and rights of subjects For studies with greater than minimal risk an independent data monitor will be assigned to monitor the study data and for high-risk studies an independent data safety monitoring committee will be established to monitor the accumulated safety data and efficacy data to make recommendations on whether to proceed with the study
6Ethics of clinical research Clinical studies will follow the Declaration of Helsinki and other relevant regulations of the World Medical Assembly The study can only be carried out after the approval of the study by the ethics committee before the start of the study Before each subject is enrolled in this study the investigator has the responsibility to fully and comprehensively introduce the purpose procedures and possible risks of this study to the subject or his agent and sign a written informed consent form and the subject should be let know that they have the right to withdraw from this study at any time and the informed consent should be retained as a clinical study document for future reference The privacy and confidentiality of the subjects will be protected during the study
Coenzyme I nicotinamide adenine dinucleotide NAD Is a very important coenzyme in biological redox reactions and plays a crucial role in various biological processes including metabolism senescence cell death DNA repair and gene expressionNADMetabolic abnormalities are closely related to the occurrence and development of many diseases including cancer On November 92020 Academician Wang Hongyangs team published the title NAD on Cell Metabolismmetabolism maintains inducible PD-L1 expression to drive tumor immune evasion research paper reveals the NADMetabolism drives novel mechanisms of tumor immune escape by regulating immune checkpoint PD-L1 expression and is proposed by supplementing NADNovel strategies to enhance therapeutic sensitivity of anti-PD-1 PD-L1 antibodies5 Further studies found that the anti-PD-1 antibody suppressed tumor burden by 422 in a model of Hep 1-6-CD38 immunotherapy administered NADThe tumor burden suppression rate after the combination therapy was 828 In the primary tolerance model of Pan02 immunotherapy in pancreatic cancer the anti-PD-1 antibody suppressed tumor burden by only 186 giving NADThe combined treatment tumor burden suppression rate was 647 In both models simultaneously the NADThe group alone did not promote tumor growth compared with the control group The study has important clinical implications to complement the NADA combination regimen with anti-PD-1 PD-L1 antibodies could provide a novel therapeutic strategy for tumors resistant to immunotherapy
2Effectiveness evaluation indicators primary efficacy indicators and secondary efficacy indicators Primary endpoint
ORR as assessed by mRECIST 11 Selected secondary study endpoints and exploratory endpoints
Safety and tolerability
DOR DCR PFS TTP OS as assessed by mRECIST 11
Conversion rate Safety evaluation index The incidence and severity of all adverse events AEs treatment emergent adverse events TEAEs grade 3 or higher study drug-related adverse events serious adverse events SAEs were judged according to CTCAE V50 and the clinical characteristics severity time of occurrence of any adverse events were recorded End time duration treatment measures and outcomes and determine their relevance to treatment regimens
3Statistical Methods All statistical analyses will be performed in SAS 94 or later In general continuous variables will be statistically described using the number of cases mean median standard deviation minimum and maximum values Categorical and hierarchical variables will be statistically described using the frequency and percentage of each category or grade and missing values will not be included in the calculation of percentages unless otherwise indicated Unless otherwise stated all statistical tests will be performed using a two-sided test of α 005 with a two-sided 95 confidence interval CI calculated
4Statistical processing All statistical analyses will be performed using SAS 94 or later In general continuous variables will be statistically described using the number of cases mean median standard deviation minimum and maximum values Categorical and hierarchical variables will be statistically described using the frequency and percentage of each category or grade and missing values will not be included in the calculation of percentages unless otherwise indicated Unless otherwise stated all statistical tests will be performed using a two-sided test of α 005 with a two-sided 95 confidence interval CI calculated
5Data security monitoring The clinical study will develop a data security monitoring plan according to the size of the risk All adverse events are recorded in detail properly handled and tracked until properly resolved or the condition is stable and serious adverse events and unexpected events are reported to the ethics committee competent authorities and drug regulatory departments in a timely manner in accordance with regulations The principal investigator conducted a systematic review of all adverse events on a regular basis and convened investigator meetings to assess the risks and benefits of the study if necessary Double-blind trials can be urgently unblinded if necessary to ensure the safety and rights of subjects For studies with greater than minimal risk an independent data monitor will be assigned to monitor the study data and for high-risk studies an independent data safety monitoring committee will be established to monitor the accumulated safety data and efficacy data to make recommendations on whether to proceed with the study
6Ethics of clinical research Clinical studies will follow the Declaration of Helsinki and other relevant regulations of the World Medical Assembly The study can only be carried out after the approval of the study by the ethics committee before the start of the study Before each subject is enrolled in this study the investigator has the responsibility to fully and comprehensively introduce the purpose procedures and possible risks of this study to the subject or his agent and sign a written informed consent form and the subject should be let know that they have the right to withdraw from this study at any time and the informed consent should be retained as a clinical study document for future reference The privacy and confidentiality of the subjects will be protected during the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None