Clinical Trial Platform Research Articles

Early prevention of cognitive impairment in the community population: The Beijing Aging Brain Rejuvenation Initiative.

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence-based health-care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community-based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community-based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2- or 3-year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age.

Abstract PS6-05: Impact of body mass index on pathological complete response after neoadjuvant chemotherapy: Results from the I-SPY 2 trial

Abstract Purpose: Increased body mass index (BMI) is a risk factor for breast cancer and has been associated with poor outcomes in both premenopausal and postmenopausal breast cancer patients. Several retrospective studies have demonstrated higher BMI to be associated with inferior pathological complete response (pCR) to neoadjuvant chemotherapy, yet it remains unclear if this difference is related to chemotherapy underdosing among obese breast cancer patients. We evaluated the association between BMI and response to neoadjuvant chemotherapy (defined by pCR) in the I-SPY 2 trial, an adaptive clinical trial platform enrolling biologically high-risk breast cancer patients (triple negative, human epidermal growth factor receptor 2 (HER2) positive and MammaPrint high-risk) that utilizes standard neoadjuvant therapy regimens with treatment based on actual body weight. Patients and Methods: From 3/2010 to 11/2016, 989 patients were enrolled in the I-SPY 2 trial, 978 had a recorded baseline BMI prior to treatment and were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI>=30 kg/m2), overweight (25=<BMI<30 kg/m2), and normal or underweight (<25 kg/m2) based on World Health Organization criteria. pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR, and we reported odds ratios (OR) and 95% confidence intervals (CI). Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. Results: The median age in our study population was 49 years. 35% of patients were normal/underweight, 32% overweight, and 33% obese. Black patients were more likely to be obese (P<0.0001). pCR rates differed significantly by tumor subtype (P<=0.0001) and tumor stage (P=0.0009). pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariate analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR to neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR=1.1, 95%CI: 0.68-1.63, p=0.83), and for overweight compared with normal/underweight (OR=1, 95%CI: 0.64-1.47, p=0.88). We tested for potential interaction between BMI and breast cancer subtype, however, the interaction was not significant in the multivariate model (P=0.09) (Table 1). Multivariate Cox regression showed there was no difference in EFS (p=0.81) or OS (p=0.52) between obese, overweight and normal/underweight breast cancer patients with a median follow-up time of 4.0 years. Conclusions: There was no difference in pCR rates by BMI with actual body weight based neoadjuvant chemotherapy in this biologically high-risk breast cancer population. In contrast, breast cancer subtype and stage showed predictive value for pCR in this high-risk operable breast cancer population receiving neoadjuvant chemotherapy in the I-SPY 2 clinical trial. Table 1: pCR rate of different BMI categories by breast cancer subtypes.Breast Cancer SubtypepCRNormal/underweight Frequency (%)OverweightFrequency (%)ObeseFrequency (%)P-valueHR+/HER2+No39 (61.9)27 (61.4)32 (66.7)0.83Yes24 (38.1)17 (38.6)16 (33.3)HR+/HER2-No105 (80.8)116 (89.2)93 (78.8)0.06Yes25 (19.2)14 (10.8)25 (21.2)HR-/HER2+No7 (25.0)11 (35.5)15 (51.7)0.11Yes21 (75.0)20 (64.5)14 (48.3)HR-/HER2-No83 (65.4)58 (55.8)76 (60.8)0.33Yes44 (34.7)46 (44.2)49 (39.2)(HR: hormone receptor, HER2: human epidermal growth factor receptor 2) Citation Format: Haiyun Wang, Douglas Yee, David Potter, Patricia Jewett, Christina Yau, Heather Beckwith, Allison Watson, Nicholas G O'Grady, Amy Wilson, Susie Brain, I-SPY 2 TRIAL Consortium, Anne Blaes. Impact of body mass index on pathological complete response after neoadjuvant chemotherapy: Results from the I-SPY 2 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-05.

The Effects of Antibiotics for Helicobacter pylori Eradication or Dapsone on Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Background: Chronic spontaneous urticaria (CSU) is a disease with wheals and/or angioedema. Some drugs, especially antibiotics for Helicobacter pylori (H. pylori) eradication and the sulfone antibiotic dapsone, may be candidates for treating CSU. The present study assessed the efficacy of these antibiotic therapies for CSU. Methods: Databases (MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched until October 2020. Study selection, data abstraction and quality assessments were independently performed using the Grading of Recommendations Assessment, Development and Evaluation approach. The outcomes were the remission of CSU-related symptoms, activities and adverse events due to antibiotics for H. pylori eradication or dapsone. Results: Nine randomized controlled trials (RCTs; 361 patients) were included. The antibiotics for H. pylori eradication increased the remission rate (risk ratio (RR) = 3.99, 95% confidence interval (CI) = 1.31 to 12.14; I2 = 0%), but dapsone did not (RR = 1.15, 95% CI = 0.74 to 1.78). Antibiotics for H. pylori eradication (standard mean difference (SMD) = 1.49, 95% CI = 0.80 to 2.18; I2 = 69%) and dapsone (SMD = 7.00, 95% CI = 6.92 to 7.08; I2 = 0%) improved symptoms. The evidence of certainty was moderate. Dapsone was associated with mild adverse events, whereas H. pylori eradication was not. Conclusion: Antibiotics, especially those for H. pylori eradication, improved the remission rate and symptoms of CSU with few adverse events. Further studies are needed.

NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC)—Pembrolizumab experimental arm (EA) primary results.

8 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel EAs in LARC. EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk pt population with correlative biomarkers. Here we report the primary and available secondary endpoints (EPs). Methods: Stage II/III LARC pts (with ONE or more of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy +/- pembrolizumab 200mg IV Q3 wks x 6 doses) → surgery 8-12 wks following last dose of radiotherapy. Primary EP: Improvement in Neoadjuvant Rectal Cancer (NAR) score for EA v control potentially representing a 3-4% absolute OS improvement. Secondary EPs: Comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter sparing surgery (SSS), and exploratory assessments of molecular and radiographic predictors of response and distant failure. Binary EPs compared by Fisher’s exact test. Reported p-values are two-sided. Results: From 8/2018-5/2019, 185 pts were randomized to control (n=95) or pembrolizumab (n= 90). Baseline characteristics were relatively well balanced. 137 pts were evaluable for NAR (68 control, 69 pembrolizumab). Mean NAR was 14.08 for control (95% CI: 10.7-17.4) v 11.53 for pembrolizumab (CI: 8.5-14.6) (p=0.26). pCR=29.4% v 31.9% (p=0.75); cCR=13.6% v 13.9% (p=0.95); and SSS=71.0% v 59.4% (p=0.15). The side effects on Arm 3 were consistent with both CRT and pembrolizumab safety profile. Grade 3/4 AEs were slightly increased on the pembrolizumab arm during and after CRT (48.2 v 37.3%). There were 2 deaths during FOLFOX, one on the control arm due to sepsis; the other on the EA due to pneumonia. There were no statistically significant differences in RT (fractions, dose, boost fractions, or boost dose), FOLFOX or capecitabine doses. Conclusions: Pembrolizumab added to chemoRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. The secondary endpoints including PFS and OS have not been reached. Correlative analysis for both T-cell and myeloid cell populations in the tissue and blood in addition to comprehensive cytokine analysis is ongoing. NCT02921256. Support: U10CA180868, -180822; UG1-189867; U24-196067. Clinical trial information: NCT02921256.

Senior-COVID-Rea Multicentre Observational Cohort Study: Development of a Geriatric Prediction Model of Day 30 Mortality in Patients Over 60 in ICU

Background: Current SARS-COV2 pandemic induces tensions on the health systems and ethical dilemmas. A triage tool is needed to define older patients with individual advantage to be considered for intensive care unit (ICU) transfer.Methods: This multicentre observational cohort study included patients over 60 admitted into 7 ICUs between 7th March and 7th May 2020. The primary objective was to evaluate age impact on 30-day mortality, to construct a multivariate prognostic model. This analysis explores the prediction value of geriatric parameters 1 month before ICU admission. This trial is registered with ClinicalTrials.gov, number NCT04422340.Findings: Among 290 screened patients, 231 were included in the cohort. In univariate analysis, factors associated with decreased day-30 survival were: age>75 (OR 4·82 [95%CI: 2·56-9·06]), three or more CIRS-G grade ≥2 comorbidities (OR 2·49 [95%CI: 1·36-4·56]), impaired ADL (Activities of Daily Living), (OR 4·86 [95%CI: 2·44-9·72]), impaired IADL8 (Instrumental ADL, 8 variables, OR 6·33 [95%CI: 3·31-12·10], p75 (OR 4·64 [95%CI: 2·36-9·39], pInterpretation: Age and IADL8 provide independent prognostic factors for day-30 mortality in patients over 60 admitted in ICU for severe COVID-19 infection. Our triage model proposes 3 classes of day-30 mortality risks: 8-14% for patients younger than 80 with no impairment in IADL, 30-40% for patients either younger than 70 with at least one impairment in IADL8 or older than 80 with no impairment in IADL and 67-88% for patients over 80 with at least one impairment in IADL.Trial Registration: ClinicalTrials platform on June 9, 2020 (NCT04422340).Funding Statement: Hospices Civils de LyonDeclaration of Interests: All the authors declare grants from Hospices Civils de Lyon, during the conduct of the study, no other competing interests with the considered topic. CF reports outside of the present work consulting/advisory roles for GSK, Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen, and Novartis; research funding from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma; and travel/accommodation/expenses from Janssen Oncology, Pierre Fabre, and Leo Pharma.Ethics Approval Statement: The study protocol (V1.0 of April 7, 2020) was approved by a COVID-19-dedicated Ethics Committee of the Hospices Civils de Lyon on May 12, 2020.

A Permissioned Blockchain-Based Clinical Trial Service Platform to Improve Trial Data Transparency.

The clinical research faces numerous challenges, from patient enrollment to data privacy concerns and regulatory requirements to spiraling costs. Blockchain technology has the potential to overcome these challenges, thus making clinical trials transparent and enhancing public trust in a fair and open process with all stakeholders because of its distinct features such as data immutability and transparency. This paper proposes a permissioned blockchain platform to ensure clinical data transparency and provides secure clinical trial-related solutions. We explore the core functionalities of blockchain applied to clinical trials and illustrate its general principle concretely. These clinical trial operations are automated using the smart contract, which ensures traceability, prevents a posteriori reconstruction, and securely automates the clinical trial. A web-based user interface is also implemented to visualize the data from the blockchain and ease the interaction with the blockchain network. A proof of concept is implemented on Hyperledger Fabric in the case study of clinical management for multiple clinical trials to demonstrate the designed approach's feasibility. Lastly, the experiment results demonstrate the efficiency and usability of the proposed platform.

Platform Trials to Expedite Drug Development in Alzheimer\u2019s Disease: A Report from the EU/US CTAD Task Force

A diverse range of platforms has been established to increase the efficiency and speed of clinical trials for Alzheimer’s disease (AD). These platforms enable parallel assessment of multiple therapeutics, treatment regimens, or participant groups; use uniform protocols and outcome measures; and may allow treatment arms to be added or dropped based on interim analyses of outcomes. The EU/US CTAD Task Force discussed the lessons learned from the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) platform trial and the challenges addressed by other platform trials that have launched or are in the planning stages. The landscape of clinical trial platforms in the AD space includes those testing experimental therapies such as DIAN-TU, platforms designed to test multidomain interventions, and those designed to streamline trial recruitment by building trial-ready cohorts. The heterogeneity of the AD patient population, AD drugs, treatment regimens, and analytical methods complicates the design and execution of platform trials, yet Task Force members concluded that platform trials are essential to advance the search for effective AD treatments, including combination therapies.

Research Evaluation Alongside Clinical Treatment in COVID-19 (REACT COVID-19): an observational and biobanking study

IntroductionThe COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthcare services. Earlier identification of patients at risk of severe disease may allow intervention with experimental targeted treatments, mitigating...

Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines

SummaryTrial Design: An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B. Methods67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old. Inclusion Criteria: NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 μg doses (two complete guidelines). The objective of this study was to provide Health workers-staff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix® dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking. ResultsThe participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix®, administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix®. 57.14% (12 out 21) had a positive response to second dose of Fendrix®. 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix®. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix®. No serious adverse event occurred. ConclusionsThe use of Fendrix®, is a viable vaccine alternative for NHS workers classified as “non-responders”. Revaccination of healthy non-responders with Fendrix®, resulted in very high proportions of responders without adverse events.Trial registration: The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23).Funding: GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013–2016 and co-financed by and the European Regional Development Fund (ERDF).

Early vs. Delayed Feeding after Endoscopic Submucosal Dissection for Gastric Cancer: A Systematic Review and Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) for gastric cancer is increasingly performed worldwide due to its efficacy and safety. This study aimed to assess the evidence of the impact of early vs. delayed feeding after ESD on quality of care, which remains to be fully determined. Methods: Electronic databases (PubMed, the Cochrane Central Register of Controlled Trials, EMBASE) and the trial registries (the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched for studies performed prior to September 2020. Study selection, data abstraction, and quality assessment were independently performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Self-rated satisfaction and hospital stay were chiefly analyzed. Results: Two randomized controlled trials (239 patients) were included. The early and delayed post-ESD feeding groups had similar rates of post-ESD bleeding (risk ratio 1.90, 95% CI 0.42 to 8.63; I2 = 0%). Early post-ESD feeding resulted in increased patients’ satisfaction in comparison to delayed post-ESD feeding (standard mean difference (MD) 0.54, 95% CI 0.27 to 0.81; I2 = 0%) and reduced the length of hospital stay (MD −0.83, 95% CI −1.01 to −0.65; I2 = 0%). Conclusion: Early post-ESD feeding was associated with increased patients’ satisfaction and reduced hospital stay in comparison to delayed feeding, while the rate of complications did not differ to a statistically significant extent. As we must acknowledge the limited number of reviewed studies, various trials regarding the quality of care are further needed to determine the benefits of early feeding after ESD.

Abstract IA-12: Precision oncology for pancreatic cancer

Abstract Pancreatic cancer presents distinct challenges in advancing more contemporary therapeutic approaches that target specific molecular aberrations within subgroups of patients. This “precision oncology” approach requires: 1. The ability to define targetable molecular pathology and the characteristics of molecular subtypes which harbour vulnerabilities and build preclinical platforms of evidence that support the testing of therapeutic strategies in clinical trials.2. The capability and capacity to accurately select subgroups of participants and provide feasible opportunities for clinical trials of novel therapeutic strategies in the real world.3. The ability to robustly aggregate data from clinical trials and cohorts to inform the evolution of novel therapeutic approaches. To achieve these goals, the Glasgow Precision Oncology Laboratory has endeavoured to define molecular vulnerabilities and build the systems that enable the above 3 requirements. The Glasgow Cancer Test The GPOL team have created a new suite of tests that not only covers what is already known about cancer, but also allows for new information to be assimilated. The content of the GCTs is carefully curated to include genomic features for which there is high-quality objective evidence for a biological role in cancer. These genomic features are tiered by clinical actionability and confidence to generate a nested set of cancer assays to accommodate different clinical or scientific requirements and financial and infrastructure constraints so as to meet increasing demand, especially in cancers of unmet need. Precision-panc Precision-Panc was designed to be the evolution of clinical trial platforms that involved molecular profiling for difficult to treat cancers, typically not a priority for commercial therapeutic development. It was developed in partnership with, and has significant funding support from industry. In order to institute a step change for pancreatic cancer, it was necessary to transform pancreatic cancer therapeutic development into a more competitive arena so as to secure greater investment from pharmaceutical companies. Essential to this strategy is the concept that molecular profiling of all cancer patients should be performed for clinical trials (Reasons to be testing: the dawn of complex molecular profiling in routine oncology practice. Beer et al. Ann Oncol. 2019 30:1691-1694). In the area of human data science, extremely accurate information from digital pathology and digital imaging necessitates the molecular profiling of cancer coupled with accurate clinical data at scale and is the long-term goal of the processes developed through Precision-Panc. From commencement of funding, the first site was open within 8 months, with the first randomisation a month after that. From first randomisation, after 2 years, 26 sites have been opened, 277 participants have entered the platform, 216 registered for studies and 113 proceeded to a trial. Current rate of participant entry into Precision-Panc is 15 - 20 per month. Of the 6 specific trials currently on the platform, one has completed, 5 continue with more in development in order to accommodate all therapeutic opportunities (eg:metastatic, 2nd-line, local advanced, resectable disease). ICGC-ARGO The International Cancer Genome Consortium’s new initiative called ARGO (Accelerating Research in Genomic Oncology) designed and led by GPOL aims to deliver a Million patient years of precision oncology knowledge. Platforms such as Precision-panc will contribute data to ICGC-ARGO to enable pooled analysis of granular standardised datasets across and between different cancer types. Citation Format: Andrew V. Biankin. Precision oncology for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-12.

Inhibit Clinical Trials Platform to Prevent and Eradicate Inhibitors: Feasibility Survey of Current Prophylaxis and Immune Tolerance Practices

Inhibit Clinical Trials Platform to Prevent and Eradicate Inhibitors: Feasibility Survey of Current Prophylaxis and Immune Tolerance Practices

Informing prevention of stillbirth and preterm birth in Malawi: development of a minimum dataset for health facilities participating in the DIPLOMATIC collaboration

ObjectiveThe global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm...

Accuracy of plain radiography in detecting fractures in older individuals after low-energy falls: current evidence.

BackgroundOlder individuals sustaining low-energy falls (LEF) and presenting to the emergency department (ED) demand straightforward diagnostic measures for injury detection. Plain radiography (XR) series for diagnosis of fall-related injuries are standard of care, but frequently subsequent CT examination is required for diagnostic assurance. A systematic database search of diagnostic accuracy of XR for detection of fractures in older LEF patients was performed.MethodsWe searched PubMed, Embase, Cochrane Library, WHO International Clinical Trial Platform, and Clinical trials.gov databases from inception to January 2020 for studies including older patients (≥65 years) with LEF and obtaining CT examination and XR of the skeleton in an ED setting.ResultsFrom 8944 references screened, 11 studies met the criteria for inclusion. Performance of XR for detection of fractures of the pelvic ring and hip was analyzed in nine studies, two studies investigated XR performance to detect rib fractures, and two studies compared diagnostic accuracy of thoracolumbar spine XR. Sensitivity estimates ranged from 10% to 58% and specificity estimates from 55% to 100%. Clinical and statistical heterogeneity was significant among included studies, with an overall considerable risk of bias.DiscussionHigh-quality evidence on accurate imaging strategies in older patients with LEF is lacking to date. XR is missing a reasonable amount of fractures of the pelvic ring, rib cage, and thoracic and lumbar spine. However, the utility of first-line CT imaging and the benefit of diagnosing every fracture is unknown, demanding high-quality prospective trials considering patient-oriented outcome as well.

Broad Adaptive Pancreatic Clinical Trial Platform Launched

Broad Adaptive Pancreatic Clinical Trial Platform Launched

Identification and analysis of ongoing registered clinical intervention trials on COVID-19.

The World Health Organization declared the disease caused by the novel coronavirus (SARS-CoV-2), a pandemic on March 11, 2020. Several studies have been proposed and started since then, mainly covering prevention, diagnosis, management, and treatment. To identify and categorize all intervention studies up to the end of May related to SARS-CoV-2 infection, according to population and geo-graphical location (emphasis in Latin America) and to verify if there is any correlation according to purpose, phase, and recruitment status. One thousand six hundred seventy-two trials were selected from 1705 until May 24 on the World Health Organization clinical trials platform related to COVID-19. Jupyter and Python tools were used for data processing and cleaning. One thousand six hundred seventy-two intervention studies related to SARS-CoV-2 infection were found. China, The United States, Iran, France, and Spain are the countries participating in the largest number of studies, while only 4,1% are from Latin America (mostly Brazilian). 28 studies are focusing only on older adults, and ten studies are based exclusively on populations under 19 years of age. The worldwide interest in this new disease is reflected in the increasing number of intervention studies that are being carried out to date. How-ever, the studies analyzed do not cover the most vulnerable age groups proportionally and do not have equitable participation of all the coun-tries. In Latin America, this problem is exacerbated by the region's social, economic, and political limitations. Because it is an emerging disease, there is still not enough information to establish strong correlations between the analyzed variables, and the standardization of protocols is not yet definite because most of the studies are in progress.

CONGENITAL MUSCULAR DYSTROPHIES: P.193 Collagen VI-related myopathy. Clinical and genetic findings in a large Chilean cohort

Collagen VI related myopathy is one of the more prevalent inherited neuromuscular myopathies. Determining the genetic and clinical features in our population is relevant to improve patients care and develop a platform for collaborative studies and future clinical trials. We describe the phenotype, genotype and muscle MRI (WBMRI) in a series of patients with Collagen VI-Related Myopathy (COLVI-RM). A retrospective study of patients with a genetic diagnosis of Collagen-VI-RM, IRB-approved. Demographic data and patients’ characteristics were obtained from medical records.

Meditation as an approach to lessen menopausal symptoms and insomnia in working women undergoing the menopausal transition period: A randomized controlled trial

ObjectiveThe objective of this study was to assess the impact of meditation (Raja Yoga meditation) on insomnia and other menopausal symptoms experienced by working women during the menopausal transition period. MethodA randomized clinical trial was conducted with 47 women between the ages of 40 and 55 who worked in three of the National Institute of Social Security units, in the city of Sao Paulo, Sao Paulo, Brazil. Participants were randomized into two groups: an intervention group, who practiced Raja Yoga Meditation and Sleep Hygiene - M + SH (n = 18); and a control group, who practiced only Sleep Hygiene - SH (n = 15) during a period that went from April to July 2013. Eight weekly meetings were held with the participants of both groups. Menopausal symptoms and sleep disturbances were the outcomes analyzed. ResultsIn relation to the intensity of the insomnia symptom, improvement in relation to time was observed in both groups (M + SH p = 0.001) (SH p = 0.005). The intervention group showed a significant improvement in KMI index (p = 0,024). The control group showed improvement in PSQ total score (p = 0,016). In the comparison between groups ANOVA two-way test showed significant difference (0,026) in KMI, demonstrating that meditation can be relevant for the decrease of climatic symptoms. ConclusionThe results suggest that Raja Yoga meditation may be a non-pharmacological alternative in the control of sleep quality and menopause associated symptoms during late menopausal transition, contributing to the improvement of working women’s quality of life. Registered in the Brazilian Clinical Trials Platform UTN: U1111−1136-0744.

Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project.

PurposeNext-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations.Materials and MethodsAs of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy.ResultsIn 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors.ConclusionK-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

Abstract 3620: Actionable genomic landscape of metastatic colorectal cancer patients in Korea: Interim data from K-MASTER project

Abstract The K-MASTER cancer precision medicine diagnosis and treatment enterprise (K-MASTER project) is a precision medicine cancer treatment clinical trial platform, which uses NGS assay to screen the actionable mutations in 10,000 Korean patients with refractory solid tumors and assigns the patients to matched clinical trials. K-MASTER project was initiated at June 2017 and 52 sites, 4930 patients have participated. As of November 30 in 2019, total 889 metastatic colorectal cancer (mCRC) patients were submitted. Tumor DNA was analyzed by FIRST cancer panel (Seoul National University Hospital) and CancerSCAN (Samsung Genomic Institute) which allow to detect variations of 183 and 409 genes irrespectively. The failure rate of sequencing was 5.5% of patients with samples submitted. The mean depth was 650x (FIRST) and 701x (CancerSCAN). Average turn-around time was 3 weeks (CancerScan) and 6 weeks (FIRST). In Korean mCRC patients, variations were mainly identified in TP53 (60.9%), APC (56.9%), KRAS (41.4%), BRCA2 (19.2%), PIK3CA (14.5%), ATM (14.2%), KMT2D (13.4%), NOTCH1(13.4%), SMAD4 (11.6%), FBXW7 (10.2%), ALK (9.7%), NOTCH3 (9.2%), BRAF (8.8%). MSI-high or POLE mutant mCRC patients were enrolled in KM-01 (Avelumab). Several drugs were already approved in the other countries but not in Korea; ERBB (7.5%) with anti-HER2 agents, and MSI high such as MSH6 (3.9%), MSH2 (3.7%), MLH1 (3.4%) with immune checkpoint inhibitors. In addition, there were potentially actionable variants outside of approved label in Korea; translocation of NTRK3 (n=4), RET (n=3), ALK/EML4 (n=2). Promising drugs could be possible to incorporate in clinical trials using PIK3CA (14.5%) with PIK3CA/Akt/mTOR pathway inhibitor, DNA damage response (DDR) genes such as BRCA2 (19.2%), ATM (14.2%), FANCA (6.6%), POLE (5.8%), BRIP1(4.8%), RAD50 (4.5%), BRCA(4.0%), PALB2 (4.0%), PARP2 (3.7%), CDK12 (3.4%), MUTYH (2.7%), RAD54L (2.5%) with immune checkpoint inhibitor and/or PARP inhibitor, KRAS G12C (n=18) with AMG 510 (KRAS inhibitor), amplification of FGFR1 (n=4) and MET (n=1). There are 2 clinical trials which mCRC patients can participate in early 2020; MET alteration in KM-08 (Tepotinib), high tumor mutation burden in KM-12 (Ipilimumab and nivolumab). In conclusion, this project is efficient to detect actionable variations in mCRC. This novel knowledge provides an intriguing background to investigate new clinical trials with biomarker and give therapeutic opportunity for mCRC patients. By help of regulatory approval of innovative drugs and off-label use, biomarker-driven early phase clinical trials, it could be a huge therapeutic opportunity for refractory mCRC patients. (This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp;Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Yoon Ji Choi, Won Jin Chang, Ju Won Kim, Kyong Hwa Park, Yeul Hong Kim. Actionable genomic landscape of metastatic colorectal cancer patients in Korea: Interim data from K-MASTER project [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3620.