Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Quality Management Model for Phase I Clinical Drug Trials:A Structural Equation Model

This study aimed to construct a quality management model for phase I clinical drug trials.A cross-sectional survey was conducted and data were collected from 604 respondents at 69 institutions in China engaged in phase I clinical drug trials.Exploratory and confirmatory factor analyses were used to develop the survey tool.Structural equation modeling was used to construct a quality management model for phase I clinical drug trials.The results showed that the final survey tool had good reliability and validity(Cronbach’sα=0.938,root mean square error of approximation=0.074,comparative fit index=0.962,and Tucker—Lewis index=0.955).The model included five dimensions:government regulation,industry management,medical institution management,research team management,and contract research organization(CRO)management.In total,22 measurement items were obtained.The structural equation model indicated government regulation,industry management,medical institution management,and CRO management significantly affected the quality of phase I clinical drug trials(β=0.195,β=0.331,β=0.279,andβ=−0.267,respectively;P<0.05).Research team management had no effect on the quality of trials(β=0.041,P=0.610).In conclusion,the model is valuable for identifying factors influencing phase I clinical drug trials and guiding quality management practices.

Specification of phase Ⅰ of new drugs' clinical tolerance trials

Phase Ⅰ of clinical trials is the first stage of clinical pharmacology and body safety evaluation,including body tolerance test and pharmacokinetics test.The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase Ⅱ of clinical trials.This text discussed the technique and requirement of phase Ⅰ of new drugs' clinical tolerance trials.

PHASE II CLINICAL TRIAL OF LASTET CAPSULE IN COMBINATION CHEMOTHERAPY OF MALIGNANT TUMORSIN CHINA

This study reports the efficacy of prolonged administration of oral etoposide in the treatment of 86 cases with solid tumor,malignant lymphoma and other cancer.The oral etoposide used was the Lastet capsule (Las-c).An overall response rate(RR)of 62.8% was achieved with CR rate being 23.3% and PR rate 39.5%. Different combination chemotherapy regimens led to different response rates but no significant difference was found. The Las-C containing regimens used in this study have not caused any serious side effects.

Clinical Trial Phases

Developers of drugs, biologicals, and medical devices must ensure product safety, demonstrate medical benefit in people, and mass produce the product. Preclinical development starts before clinical trials and the main goals are to determine safety and effectiveness of the intervention. If preclinical studies show that the therapy is safe and effective, clinical trials are started. Clinical trial phases are steps in the research to determine if an intervention would be beneficial or detrimental to humans and include Phases 0, I, II, III, IV, and V clinical studies. Understanding the basis of clinical trial phases will help researchers plan and implement clinical study protocols and, by doing so, improve the number of therapies coming to market for patients.

热淋清颗粒治疗尿路感染的多中心、开放性、Ⅳ期临床研究

目的评价热淋清颗粒在临床使用中的安全性与有效性,以指导优化临床给药方案和提高合理用药水平。方法在51家医院进行开放性、Ⅳ期临床试验,受试者为下焦湿热型单纯性或复杂性尿路感染,单纯性尿路感染患者给予热淋清颗粒每次8 g、每天3次,疗程5 d。复杂性尿路感染患者给予热淋清颗粒每次8 g、每天3次,同时联合喹诺酮类抗生素,疗程7~14 d。结局指标为临床疗效、中医证候疗效、细菌清除率以及安全性。结果共纳入2009例受试者,其中11患者失访脱落。全分析集纳入1998例,其中单纯性尿路感染患者1532例,复杂性尿路感染患者466例。临床治愈率为68.57%,单纯性和复杂性尿路感染患者分别为74.41%和49.36%。中医证候痊显率为72.22%,单纯性和复杂性尿路感染患者分别为75.13%和62.66%。单纯性尿路感染中细菌培养阳性者的细菌转阴率为57.75%,细菌清除率为58.02%;复杂性尿路感染中细菌培养阳性者的细菌转阴率为45.59%,细菌清除率为43.92%。药物相关的不良反应发生24例次,其中单纯性尿路感染17例次,复杂性尿路感染7例次。结论热淋清颗粒治疗单纯性尿路感染的有效性和安全性较好,也可改善下焦湿热证中医证候。

Using Intelligent Screening Service Platform(ISSP)to Improve the Screening Process of Clinical Trial Subjects during COVID-19 Pandemic:An Experimental Study

Background:During the COVID-19 pandemic,clinical trial recruitment could not be carried out due to travel restrictions,transmission risks and other factors,resulting in the stagnation of many ongoing or upcoming clinical trials.Objective:An intelligent screening tool was developed using artificial intelligence technology to rapidly prescreen potential patients for phase I solid tumor drug clinical trials.Methods:A total of 429 screening process records were collected from 27 phase I solid tumor drug clinical trials at the First Affiliated Hospital of Bengbu Medical College from April 2018 to May 2021.Features of the experimental data were analyzed,and the collinearity(principal component analysis)and strong correlation(χ^(2)test)among features were eliminated.XGBoost,random forest,and naive Bayes were used to determine the weight importance of the features.Finally,prescreening models were constructed using a classification machine learning algorithm,and the optimal model was selected.Results:Among the 429 screening records,33 were generated by repeated subject participation in different clinical trials,and of the remaining 396 screening records,246(62.12%)were screened successfully.The gold standard for subject screening success was the final judgment made by the principal investigator(PI)based on the clinical trial protocol.A Venn diagram was used to identify the important feature intersections of the machine learning algorithms.After intersecting the top 15 characteristic variables of the different feature screening models,9 common variables were obtained:age,sex,distance from residence to the central institution,tumor histology,tumor stage,tumorectomy,interval from diagnosis/postoperative to screening,chemotherapy,and Eastern Cooperative Oncology Group(ECOG)score.To select the optimal subset,the 9 important feature variables were expanded to 12 and 15 feature subsets,and the performance of different feature subsets under different machine learning models was validated.The results showed that optimal performance,accuracy and practicability were achieved using XGBoost with the 12-feature subset.The final model could accurately predict the screening success rates in both internal(AUC=0.895)and external(AUC=0.796)validation and has been transformed into a convenient tool to facilitate its application in clinical settings.Subjects with a probability exceeding or equal to the threshold in the final model had a greater probability of being successfully screened.Conclusion:Based on the optimal model,we created an online prediction calculator and visualization app,the Intelligent Screening Service Platform(ISSP),which can rapidly screen patients for phase I solid tumor drug clinical trials.The IsSP can effectively solve the problems of space and time intervals.On the mobile terminal,matching between clinical trial projects and patients can be achieved,and the rapid screening of clinical trial subjects can be completed to obtain more clinical trial subjects.As an auxiliary tool,the ISSP optimizes the screening process of clinical trials and provides more convenient services for clinical investigators and patients.

Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with High-Grade Glioma. Final Report (Protocol BT-06), and Review of Recent Trials

Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.

Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.

Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession

Congestive heart failure(CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF.

A multicenter phase II trial of domestic product of zoledronic acid in the treatment of malignant hypercalcemia

Objective:To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia.Methods:A multi-center,open phase II clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min.The level of blood calcium and side effects were recorded regularly within 28 days after injection.Results:One case was dropped out due to bad compliance.The complete response rate(the corrected serum calcium was reduced to normal level)was 100.00%(14/14).The medium time of complete response rate was 5.07 days.The medium maintain time was 22.30 days.Slight,or moderate fever was observed.Conclusion:Zoledronic acid can effectively reduce the malignant hypercalcemia.The use of zoledronic acid appears to be safety and convenient.

Progress in phase III clinical trials of molecular targeted therapy and immunotherapy for glioblastoma

Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields.Accordingly,the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management.A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials.However,these drugs are ineffective for all patients,as evidenced by the fact that only a minority of patients in these trials showed prolonged survival.Furthermore,there are several published phase III clinical trials that involve immune checkpoint inhibitors,peptide vaccines,dendritic cell vaccines,and virotherapy.Accordingly,this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.

零期临床助力中国原创药研发新范式迭代

新药研发是一项耗时长且风险高的系统工程,需要投入大量资源。由于药物的安全性很难预料,药物开发失败花费的75%左右都在早期临床阶段。零期临床研究主要通过“微剂量”研究快速获得人体药代动力学及药效学等重要信息,为后期的药物临床试验节约资源,提高成功率。但在我国零期临床研究尚处于起步阶段,没有相应的法规和指导原则,缺乏合理的研究设计和专业的研究人员。本文就创新药物零期临床研究的内涵、目前存在的问题及解决策略与如何在中国有效开展零期临床等作一概述,以期为我国的原创药研发提供新范式参考。

小儿解表口服液治疗流行性感冒(风热犯卫证)多中心随机对照临床研究

目的评价小儿解表口服液治疗流行性感冒(风热犯卫证)的疗效及其安全性。方法采用分层区组随机、阳性药平行对照、多中心临床试验设计。计划纳入300例受试儿童,随机分为治疗组和对照组。治疗组予小儿解表口服液,对照组予磷酸奥司他韦颗粒,疗程5 d。比较两组疾病临床痊愈时间,完全退热时间,加拿大急性呼吸道疾病和流感量表(Canadian Acute Respiratory Illness and Flu Scale,CARIFS)评分,中医证候疗效,单项症状消失率,退热持续时间,并发症、重症及危重症发生率,和安全性指标。结果共纳入临床诊断患儿300例,其中297例进入全分析数据集(Full a⁃nalysis set,FAS),289例进入符合方案数据集(Per protocol set,PPS),297例进入安全性数据集(Safety set,SS)。治疗后,疾病临床痊愈中位时间,组间比较差异均无统计学意义(P>0.05),采用COX回归分析,按0.75的非劣标准,治疗组非劣效于对照组,PPS与FAS分析结论一致;完全退热中位时间,组间比较,FAS/PPS分析差异无统计学意义(P>0.05),采用COX回归分析,按0.75的非劣标准,治疗组非劣效于对照组;流涕消失率治疗组优于对照组,差异有统计学意义(P<0.05);PPS退热持续时间治疗组6(6~12)h,对照组6(6~7.5)h,经Log-rank检验,差异有统计学意义(P<0.05)。CARIFS评分,中医证候疗效,以及并发症、重症及危重症发生率组间比较差异均无统计学意义(P>0.05)。结论小儿解表口服液治疗儿童流行性感冒(风热犯卫证)具有缩短病程作用,疗效非劣于磷酸奥司他韦颗粒,临床应用的安全性较好。

Ⅳ期临床试验规范化管理研究

Ⅳ期临床试验在我国起步较晚,发展迅速,其研究意义和重要性也逐渐得到认可,但迅速发展的背后存在诸多应该防范的问题。明确Ⅳ期临床试验免费赠药问题、规范机构选择、扩大开展项目范围以及充分发挥机构及伦理委员会职能、强化Ⅳ期临床试验管理等方式,均可有效规范管理。

糖尿病肾病(Ⅳ、Ⅴ期)中医证候临床研究

目的:通过实验分析糖尿病肾病(Ⅳ、Ⅴ期)中医证候,准确判断糖尿病肾病患者的证候并对症诊治。方法:选取2015年5月-2017年5月某院内分泌科、肾病及保健科住院患者共100例进行实验研究,探讨糖尿病肾病的中医证候特点,分析患者的病因病机,深化患者病症与证候之间的关系,有效提升糖尿病肾病(Ⅳ、Ⅴ期)患者中医辨证分型的标准化、客观化,同时为糖尿病肾病患者的防治提供积极借鉴意义。结果:所选100例糖尿病肾病患者中,IV期62例,占62%,V期38例,占38%;IV期患者常出现的症状包括全身浮肿、大便干、小便黄且量多、口干口黏、口渴多饮、肢体麻木、神疲乏力以及少气懒言等,中医证型包括气虚、血虚以及阴阳两虚等虚证,实证包括血瘀、痰浊及水湿证;V期患者主要症状包括肢体麻木、畏寒肢冷、口干、面足浮肿及神疲乏力,中医证候主要包括气虚、阴虚、血瘀等,且血瘀证明显增加。结论:中医证候能够作为糖尿病肾病患者的临床诊断之一,确保中医证候分型的标准化、客观化能够为糖尿病肾病患者临床治疗提供积极借鉴意义,值得推广应用。

Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

GCP药师在抗肿瘤药物临床试验配置管理中的作用

目的临床试验中抗肿瘤药物的配置与普通药物不同。近年来,抗肿瘤新药临床试验越来越多,在试验过程中,抗肿瘤药物的配置管理工作也越来越重要。该文主要探讨GCP药师在Ⅱ期、Ⅲ期抗肿瘤药物临床试验配置管理中的作用,以期为同行提供经验参考。方法回顾2023年1—11月我院Ⅱ期、Ⅲ期抗肿瘤药物临床试验中的冲配工作,总结GCP药师参与Ⅱ期、Ⅲ期临床试验产生的积极作用。结果2023年1—11月的所有在研临床试验配置工作显示:①冲配临床试验药物4464袋,没有发生因冲配错误导致用药延迟的事件;②GCP药师拦截次数共19次,主要涉及药物剂量错误、冲配表单不规范等;③共发生不良反应事件314次,其中III度、IV度不良事件83次,发生次数最多的不良反应主要有眼科毒性、中性粒细胞数降低、血小板数降低及白细胞数降低等,涉及的药物主要有抗体偶联药物、紫杉醇、顺铂等;④GCP药师不断优化工作流程,制定相关SOP及标准化配置表单。结论GCP药师参与抗肿瘤药物临床试验配置管理,在方案审核、药物配置规范执行、人员防护、不良反应监测等各环节都能发挥积极的作用。同时他们可以极大地提高配置效率,有效保证输液质量,保障抗肿瘤药物临床试验用药安全。