2007年5月，世界卫生组织国际临床试验注册平台（World Health Organization International Clinical Trial Registration Platform，WHO ICTRP）正式运行，澳大利亚-新西兰临床试验注册中心（Australian and New Zealand Clinical Tria...2007年5月，世界卫生组织国际临床试验注册平台（World Health Organization International Clinical Trial Registration Platform，WHO ICTRP）正式运行，澳大利亚-新西兰临床试验注册中心（Australian and New Zealand Clinical Trials Registry，ACTR），展开更多
Background:Statins,a first-line therapeutic option for atherosclerotic cardiovascular disease(ASCVD),have prompted concerns regarding dysglycemia and diabetes,thus posing a dilemma in treating patients with prediabete...Background:Statins,a first-line therapeutic option for atherosclerotic cardiovascular disease(ASCVD),have prompted concerns regarding dysglycemia and diabetes,thus posing a dilemma in treating patients with prediabetes.Xuezhikang(XZK)decreases blood cholesterol levels without affecting glucose metabolism,and may serve as a potential substitute.Methods:The XTREME study is a prospective,randomized,open-label,multi-center trial evaluating whether XZK 1200 mg/d,compared with atorvastatin 20 mg/d,has favorable effects on HbA1c levels after 24 weeks of treatment in patients with dyslipidemia and prediabetes.After a 1-week run-in period for adherence assessment,the study will ran-domly assign(1:1)392 patients meeting the protocol inclusion criteria to one of two treatment groups:an experimental group(XZK 1200 mg/day)or a control group(atorvastatin 20 mg/day).All participants will be recruited from approxi-mately 20 Chinese medical centers.The last participant is planned to be recruited before December 2023.The primary endpoint will be change in HbA1c level from baseline to 24 weeks,or before anti-diabetic therapy initiation within 24 weeks.The key secondary outcomes will include other biomarkers reflecting blood glucose or lipid metabolism.Discussion:Delaying diabetes is desirable for individuals with prediabetes.The XTREME trial presents a unique oppor-tunity to demonstrate whether XZK might provide an alternative to statins for patients with dyslipidemia and prediabetes.展开更多
Despite advancements in several malignancies,the treatment atlas of natural killer(NK)cell therapy for pancreatic cancer remains inadequate,and the dynamic immune landscape underlying the various responses is still in...Despite advancements in several malignancies,the treatment atlas of natural killer(NK)cell therapy for pancreatic cancer remains inadequate,and the dynamic immune landscape underlying the various responses is still incompletely understood.This phase 1b/2 trial evaluated the safety and efficacy of allogeneic NK cell therapy combined with gemcitabine and S-1 as a first-line treatment for advanced pancreatic cancer(APC)and explored the dynamic responsive immune landscape(ChiCTR1900021764).The administration of 1×109 to 8×109 NK cells to 24 patients was well tolerated,with no graft-versus-host disease or dose-limiting toxicity.Among the 19 evaluable patients,the objective response rate was 31.6%,and the disease control rate was 73.7%.The median progression-free survival was 6.6 months,and the overall survival was 10.8 months.Further longitudinal single-cell RNA sequencing(scRNA-seq)of 19 paired-blood samples revealed an increased proportion of certain NK cell subsets(c4-ZEB2,c5-IL7,c6-IL15,c10-NCR3,and c11-TNFSF8)and T-cell subsets(CD8+Teff and CD4+Tem)in responders,characterized by increased expression of proinflammatory and effector molecules.Bulk T-cell receptor(TCR)Vβrepertoire sequencing of responders indicated potential T-cell clonal expansion,manifested as a greater abundance of large and hyperexpanded clonotypes.Our first-in-human trial demonstrated its safety and potentially preliminary efficacy,warranting further clinical evaluation.Multiomic profiling identified specific circulating NK and T-cell subsets potentially associated with clinical outcomes,providing novel insights into the dynamic transcriptional underpinnings of the immune landscape in response to NK cell-based therapy.展开更多
Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evalu...Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC.Participants received TACE followed by atezolizumab and bevacizumab until disease progression,unacceptable toxicity,or death.The primary endpoint was objective response rate(ORR)assessed per Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Secondary endpoints included progression-free survival(PFS),overall survival(OS),ORR by modified RECIST(mRECIST),disease control rate(DCR),time to response(TTR),duration of response(DOR),and adverse events(AEs).Between August 21,2021 and April 10,2023,45 patients were enrolled.As of the data cutoff on September 30,2024,the median follow-up was 26.7 months.The ORR was 47%per RECIST v1.1 and 67%per mRECIST.Median PFS was 17.9 months,and median OS was 33.0 months.The DCR was 87%(RECIST v1.1)and 91%(mRECIST).Median TTR was 11.9 weeks(RECIST v1.1)and 4.9 weeks(mRECIST),with median DOR of 36.6 weeks(RECIST v1.1)and 44.4 weeks(mRECIST).Of the 45 patients,44 experienced AEs of any grade,with 20 reporting grade 3-4 AEs;no grade 5 AEs were observed.TACE combined with atezolizumab and bevacizumab appears safe and feasible for intermediate-stage HCC,supporting further investigation in larger studies.展开更多
The number of clinical trials conducted in China's Mainland,including investigator‐initiated trials(IITs),has increased rapidly in recent years.However,there are few data on the characteristics of cancer‐related...The number of clinical trials conducted in China's Mainland,including investigator‐initiated trials(IITs),has increased rapidly in recent years.However,there are few data on the characteristics of cancer‐related IITs.We performed a comprehensive analysis of the landscape of cancer‐related IITs in China's Mainland in the past decade.All cancer‐related IITs registered on two clinical trial registries in the United States(www.clinicaltrials.gov,CT.gov)and China's Mainland(www.chictr.org.cn,ChiCTR)from 2010 to 2019 were identified.IITs were reviewed manually to validate classification,subcategorized by cancer type,and stratified by design characteristics to facilitate comparison across cancer types and with other specialties.A total of 8199 cancer‐related IITs were identified.The number of trials registered annually increased over time,especially in the last 5 years.Although interventional studies were predominant,randomized double‐blind studies accounted for only 8%of IITs.In the past decade,the trend for interventional studies conducted with different drugs increased year on year,although the increase in hormonal therapy IITs was not significant.Additionally,cancerrelated IITs were unevenly geographically distributed,with half concentrated in the economically developed cities Shanghai,Beijing,and Guangdong.We also found an increase in registration before participant enrollment(64.9%for trials in conducted in 2015–2019 vs.40.2%in 2010–2014,p<0.001)and data monitoring committee use(44.5%vs.40.0%,p=0.001)and a decrease in randomization(51.5%vs.62.7%,p<0.001)and funding(36.4%vs.56.3%,p<0.001)between these periods.We also observed changes in intervention type(decrease in cytotoxic drug therapy[34.8%vs.48.9%,p<0.001];increase in targeted therapy[17.8%vs.14.2%,p=0.004],immune checkpoint inhibitor therapy[6.6%vs.0.0%,p<0.001],and immune cell therapy[9.6%vs.4.5%,p<0.001]).Details of cancer‐related IITs conducted during the past decade illustrate the merits of oncology research in China's Mainland.Although the increased quantity of IITs is encouraging,limitations remain regarding the quality of clinical trials,regional imbalances,and funding allocation.展开更多
文摘2007年5月，世界卫生组织国际临床试验注册平台（World Health Organization International Clinical Trial Registration Platform，WHO ICTRP）正式运行，澳大利亚-新西兰临床试验注册中心（Australian and New Zealand Clinical Trials Registry，ACTR），
文摘Background:Statins,a first-line therapeutic option for atherosclerotic cardiovascular disease(ASCVD),have prompted concerns regarding dysglycemia and diabetes,thus posing a dilemma in treating patients with prediabetes.Xuezhikang(XZK)decreases blood cholesterol levels without affecting glucose metabolism,and may serve as a potential substitute.Methods:The XTREME study is a prospective,randomized,open-label,multi-center trial evaluating whether XZK 1200 mg/d,compared with atorvastatin 20 mg/d,has favorable effects on HbA1c levels after 24 weeks of treatment in patients with dyslipidemia and prediabetes.After a 1-week run-in period for adherence assessment,the study will ran-domly assign(1:1)392 patients meeting the protocol inclusion criteria to one of two treatment groups:an experimental group(XZK 1200 mg/day)or a control group(atorvastatin 20 mg/day).All participants will be recruited from approxi-mately 20 Chinese medical centers.The last participant is planned to be recruited before December 2023.The primary endpoint will be change in HbA1c level from baseline to 24 weeks,or before anti-diabetic therapy initiation within 24 weeks.The key secondary outcomes will include other biomarkers reflecting blood glucose or lipid metabolism.Discussion:Delaying diabetes is desirable for individuals with prediabetes.The XTREME trial presents a unique oppor-tunity to demonstrate whether XZK might provide an alternative to statins for patients with dyslipidemia and prediabetes.
基金supported by National High-level Hospital Clinical Research Funding[Grant Nos.BJ-2025-122,BJ-2023-209,and BJ-2025-151]the National Natural Science Foundation of China[Grant Nos.82373272 and 52273281]the CAMS Innovation Fund for Medical Science(CIFMS)[Grant Nos.2021-I2M-1-050].
文摘Despite advancements in several malignancies,the treatment atlas of natural killer(NK)cell therapy for pancreatic cancer remains inadequate,and the dynamic immune landscape underlying the various responses is still incompletely understood.This phase 1b/2 trial evaluated the safety and efficacy of allogeneic NK cell therapy combined with gemcitabine and S-1 as a first-line treatment for advanced pancreatic cancer(APC)and explored the dynamic responsive immune landscape(ChiCTR1900021764).The administration of 1×109 to 8×109 NK cells to 24 patients was well tolerated,with no graft-versus-host disease or dose-limiting toxicity.Among the 19 evaluable patients,the objective response rate was 31.6%,and the disease control rate was 73.7%.The median progression-free survival was 6.6 months,and the overall survival was 10.8 months.Further longitudinal single-cell RNA sequencing(scRNA-seq)of 19 paired-blood samples revealed an increased proportion of certain NK cell subsets(c4-ZEB2,c5-IL7,c6-IL15,c10-NCR3,and c11-TNFSF8)and T-cell subsets(CD8+Teff and CD4+Tem)in responders,characterized by increased expression of proinflammatory and effector molecules.Bulk T-cell receptor(TCR)Vβrepertoire sequencing of responders indicated potential T-cell clonal expansion,manifested as a greater abundance of large and hyperexpanded clonotypes.Our first-in-human trial demonstrated its safety and potentially preliminary efficacy,warranting further clinical evaluation.Multiomic profiling identified specific circulating NK and T-cell subsets potentially associated with clinical outcomes,providing novel insights into the dynamic transcriptional underpinnings of the immune landscape in response to NK cell-based therapy.
基金supported by the National Key Research and Development Program of China(2022YFC2503700,2022YFC2503705)National Natural Science Foundation of China(82473487)+2 种基金Shanghai Municipal Health Commission(2023ZZ02005)Shanghai Oriental Talents Program Youth Project(QNWS2024076)Zhejiang Provincial Key Laboratory of Medical Electronic and Digital Health(MEDH202207).
文摘Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC.Participants received TACE followed by atezolizumab and bevacizumab until disease progression,unacceptable toxicity,or death.The primary endpoint was objective response rate(ORR)assessed per Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Secondary endpoints included progression-free survival(PFS),overall survival(OS),ORR by modified RECIST(mRECIST),disease control rate(DCR),time to response(TTR),duration of response(DOR),and adverse events(AEs).Between August 21,2021 and April 10,2023,45 patients were enrolled.As of the data cutoff on September 30,2024,the median follow-up was 26.7 months.The ORR was 47%per RECIST v1.1 and 67%per mRECIST.Median PFS was 17.9 months,and median OS was 33.0 months.The DCR was 87%(RECIST v1.1)and 91%(mRECIST).Median TTR was 11.9 weeks(RECIST v1.1)and 4.9 weeks(mRECIST),with median DOR of 36.6 weeks(RECIST v1.1)and 44.4 weeks(mRECIST).Of the 45 patients,44 experienced AEs of any grade,with 20 reporting grade 3-4 AEs;no grade 5 AEs were observed.TACE combined with atezolizumab and bevacizumab appears safe and feasible for intermediate-stage HCC,supporting further investigation in larger studies.
文摘The number of clinical trials conducted in China's Mainland,including investigator‐initiated trials(IITs),has increased rapidly in recent years.However,there are few data on the characteristics of cancer‐related IITs.We performed a comprehensive analysis of the landscape of cancer‐related IITs in China's Mainland in the past decade.All cancer‐related IITs registered on two clinical trial registries in the United States(www.clinicaltrials.gov,CT.gov)and China's Mainland(www.chictr.org.cn,ChiCTR)from 2010 to 2019 were identified.IITs were reviewed manually to validate classification,subcategorized by cancer type,and stratified by design characteristics to facilitate comparison across cancer types and with other specialties.A total of 8199 cancer‐related IITs were identified.The number of trials registered annually increased over time,especially in the last 5 years.Although interventional studies were predominant,randomized double‐blind studies accounted for only 8%of IITs.In the past decade,the trend for interventional studies conducted with different drugs increased year on year,although the increase in hormonal therapy IITs was not significant.Additionally,cancerrelated IITs were unevenly geographically distributed,with half concentrated in the economically developed cities Shanghai,Beijing,and Guangdong.We also found an increase in registration before participant enrollment(64.9%for trials in conducted in 2015–2019 vs.40.2%in 2010–2014,p<0.001)and data monitoring committee use(44.5%vs.40.0%,p=0.001)and a decrease in randomization(51.5%vs.62.7%,p<0.001)and funding(36.4%vs.56.3%,p<0.001)between these periods.We also observed changes in intervention type(decrease in cytotoxic drug therapy[34.8%vs.48.9%,p<0.001];increase in targeted therapy[17.8%vs.14.2%,p=0.004],immune checkpoint inhibitor therapy[6.6%vs.0.0%,p<0.001],and immune cell therapy[9.6%vs.4.5%,p<0.001]).Details of cancer‐related IITs conducted during the past decade illustrate the merits of oncology research in China's Mainland.Although the increased quantity of IITs is encouraging,limitations remain regarding the quality of clinical trials,regional imbalances,and funding allocation.
