scholarly journals First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors

2016 ◽  
Vol 9 ◽  
pp. CGM.S39442 ◽  
Author(s):  
Barry H. Smith ◽  
Tapan Parikh ◽  
Zoe P. Andrada ◽  
Thomas J. Fahey ◽  
Nathaniel Berman ◽  
...  
Keyword(s):  
Phase 1 ◽  
Preliminary Evidence ◽  
Primary Objective ◽  
Advanced Malignancy ◽  
Agarose Beads ◽  
Potential Efficacy ◽  
Adenocarcinoma Cells ◽  
Pet Ct ◽  
Physical Examinations ◽  
Secondary Objective

Purpose Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective. Methods Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. Results RMBs were well tolerated at both dose levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related SAEs. Conclusion The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

scholarly journals The Influence of Socioeconomic Status on Snacking and Weight among Adolescents: A Scoping Review

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 167 ◽  
Author(s):  
Victoria G. Williamson ◽  
Abhaya Dilip ◽  
Jackson R. Dillard ◽  
Jane Morgan-Daniel ◽  
Alexandra M. Lee ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Scoping Review ◽  
Eating Behaviors ◽  
Preliminary Evidence ◽  
Primary Objective ◽  
Bibliographic Databases ◽  
Increased Risk ◽  
Potential Link ◽  
Secondary Objective ◽  
The Relationship

Eating behaviors, including unhealthy snacking or excessive snacking leading to excess calorie consumption, may contribute to obesity among adolescents. Socioeconomic status (SES) also significantly influences eating behaviors, and low SES is associated with increased risk for obesity. However, little is known regarding the relationship between snacking behavior and SES among adolescents and how this may contribute to obesity-related outcomes. The primary objective of this scoping review was to review the literature to assess and characterize the relationship between SES and snacking in adolescents. The secondary objective was to assess weight-related outcomes and their relation to snacking habits. Included articles were published between January 2000 and May 2019; written in English, Portuguese, or Spanish; and focused on adolescents (13–17 years). In total, 14 bibliographic databases were searched, and seven studies met the inclusion criteria. Preliminary evidence from the seven included studies suggests a weak but potential link between SES and snacking. Additionally, these dietary patterns seemed to differ by sex and income type of country. Finally, only three of the included studies addressed weight-related outcomes, but the overall available evidence suggests that snacking does not significantly affect weight-related outcomes. Due to the small number of included studies, results should be interpreted with caution.

Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4071-4071 ◽  
Author(s):  
Zev A. Wainberg ◽  
Neil Howard Segal ◽  
Dirk Jaeger ◽  
Kyung-Hun Lee ◽  
John Marshall ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Safety Profile ◽  
Phase 1 ◽  
Primary Objective ◽  
Clinical Activity ◽  
Open Label ◽  
Sorafenib Treatment ◽  
Secondary Objective ◽  
Pugh Class ◽  
Grade 3

4071 Background: Durvalumab, an anti-PD-L1 mAb, has shown early and durable clinical activity with manageable safety in an ongoing Phase 1/2, multicenter, open-label study in pts with advanced solid tumors. Interim analyses from the HCC cohort in the dose-expansion part of this study are reported here. Methods: Patients with HCC (Child-Pugh class A) received durvalumab 10 mg/kg i.v. q2w for 12 months or until confirmed progressive disease, whichever occurred first. The primary objective was to evaluate the safety profile; secondary objective was to assess the antitumor activity (investigator-assessed RECIST v1.1). Clinical activity was evaluated for the total HCC population and by viral status. Results: As of Oct 24 2016, 40 HCC pts with median 23.9 (range 2.4–34.7) weeks follow-up received durvalumab. 93% had prior sorafenib. Treatment-related AEs occurred in 80.0% of pts, most commonly fatigue (27.5%), pruritus (25.0%) and elevated aspartate aminotransferase (AST) (22.5%). Grade 3–4 treatment-related AEs were reported in 20.0% of pts, most commonly elevated AST (7.5%) and elevated alanine aminotransferase (5.0%). 7 (17.5%) pts completed the initial 12-month treatment and 7 (17.5%) pts discontinued treatment because of an AE (none related to treatment). There were no deaths due to treatment-related AEs. Clinical activity is presented in the table. 4 pts achieved a PR; 2 were ongoing at data cut-off. Conclusions: Durvalumab had an acceptable safety profile and showed promising antitumor activity and OS in pts with HCC, particularly HCV+ pts. Clinical trial information: NCT01693562. [Table: see text]

scholarly journals A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pedro M. Folegatti ◽  
Kate Harrison ◽  
Lorena Preciado-Llanes ◽  
Fernando Ramos Lopez ◽  
Mustapha Bittaye ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Chikungunya Virus ◽  
Phase 1 ◽  
Primary Objective ◽  
Open Label ◽  
Cell Responses ◽  
Single Intramuscular Injection ◽  
Secondary Objective ◽  
Vectored Vaccine

AbstractChikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.

Oral selpercatinib in pediatric patients (pts) with advanced RET-altered solid or primary CNS tumors: Preliminary results from the phase 1/2 LIBRETTO-121 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10009-10009
Author(s):  
Daniel A. Morgenstern ◽  
Leo Mascarenhas ◽  
Martin Campbell ◽  
David S. Ziegler ◽  
Karsten Nysom ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Preliminary Evidence ◽  
Primary Objective ◽  
Cns Tumors ◽  
Phase 2 ◽  
Elevated Alkaline Phosphatase ◽  
Liquid Suspension ◽  
Best Response

10009 Background: Activating RET alterations are oncogenic drivers of select pediatric and adult cancers. Selpercatinib is a first-in-class, highly selective and potent, CNS active RET kinase inhibitor. The manageable toxicity profile and durable anti-tumor activity in RET-altered cancers demonstrated in the LIBRETTO-001 phase 1/2 trial led to global approvals of selpercatinib in adults and adolescents with thyroid cancer and adults with NSCLC. Methods: LIBRETTO-121 (JZJJ) is a multicenter phase 1/2 trial in pts 0.5-21 years (yrs) of age with advanced, RET-altered solid or CNS tumors. Enrollment began in June 2019 and is ongoing. Selpercatinib is administered orally as capsule or liquid suspension BID continuously. Dosing started at the adult recommended phase 2 dose (RP2D) equivalent, 92mg/m2 BID, to confirm RP2D in pts ≤2 yrs and > 2 yrs. The phase 1 primary objective is to evaluate safety and dose limiting toxicities (DLTs). The phase 2 primary objective is to determine overall response rate by RECIST 1.1 or RANO by independent review. Results: As of 2-Oct-2020, 11 pts (6 male) aged 2–20 yrs (medullary thyroid cancer, n = 8; papillary thyroid cancer, n = 2; osteosarcoma, n = 1) had been treated (phase 1, n = 4; phase 2, n = 7). At baseline, 7 pts had measurable disease. RET alterations included fusions (n = 2), activating mutations (n = 8) and mutation with unknown clinical significance (n = 1). Prior therapies included surgery (n = 8), chemotherapy (n = 1), vandetanib (n = 1) and radiotherapy (n = 3), while 3 pts were previously untreated. Time on selpercatinib ranged from 0.9-13.4 months and 9 pts remain on treatment. One pt experienced a dose reduction and 2 pts experienced dose interruptions due to treatment-emergent adverse events (TEAEs) (elevated alanine aminotransferase [ALT] and bilirubin). There were no DLTs and no TEAEs that led to discontinuation of selpercatinib. TEAEs in > 15% of pts included elevated alkaline phosphatase (ALP), constipation, headache, elevated aspartate aminotransferase (AST), diarrhea, hyperphosphatemia, hypoalbuminemia, hypothyroidism, nausea, pyrexia, urinary tract infection, vomiting and weight gain. Drug-related TEAEs in > 15% of pts included elevated AST, elevated ALP, hyperphosphatemia and hypothyroidism. One pt reported TEAEs ≥ grade (G) 3 (elevated ALT, G3 and AST, G3) related to selpercatinib. Best response was unconfirmed partial responses in 4 pts, stable disease in 6 pts (two lasting ≥16 weeks) and progressive disease in 1 pt. Conclusions: These findings appear consistent with the adult trial results, showing preliminary evidence of safety and efficacy of selpercatinib in pediatric pts with RET-altered solid tumors. The phase 1 portion in pts ≤2 yrs and phase 2 portion at RP2D of 92mg/m2 BID for pts > 2 yrs are ongoing. Clinical trial information: NCT03899792.

The Student Room Survey: Changes in the Post Graduate Study for Cardiothoracic Surgery

2020 ◽  
Vol 23 (2) ◽  
pp. 71-74
Author(s):  
Md Faizus Sazzad ◽  
Mohammed Moniruzzaman ◽  
Dewan Iftakher Raza Choudhury ◽  
Arif Ahmed Mohiuddin ◽  
Raafi Rahman ◽  
...  
Keyword(s):  
Thoracic Surgery ◽  
Retrospective Analysis ◽  
Primary Objective ◽  
Graduate Study ◽  
Postgraduate Students ◽  
Depth Interview ◽  
Secondary Objective ◽  
Cardio Vascular ◽  
The University ◽  
Day By Day

Background: The number of postgraduate students in Cardiac surgical discipline is increasing day by day with incremental proportion are measurably suffering from the unnecessary lingering of the present course curriculum. The primary objective of this study was to find out the last 5 years’ of results of Masters in Surgery course under the University of Dhaka from a student room survey. A secondary objective was to find out positive changes that could show us the way of a step toward up-gradation. Methods: It is a retrospective analysis of all examination results of Cardio-vascular & Thoracic Surgery published since January 2008 to January 2013 from the University of Dhaka with in depth interview of 11 participants. Results: 85.24% students failed to pass part-I of Masters in Surgery for Cardio-vascular & Thoracic Surgery course while, 82.18% in part-II and 71.28% failed to pass the final part. Average 2.51 attempts needed to complete each part of the designed course resulted into lingering of course duration for 42.18 months/student. In the thoracic surgery discipline the number of students alarmingly reduced up to 0% in the recent academic sessions. Conclusions: Masters in Surgery is resulting in unnecessary prolongation of the course. We should step forward to meet the next generation challenge. Journal of Surgical Sciences (2019) Vol. 23(2): 71-74

Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study

2021 ◽  
Vol 184 (1) ◽  
pp. 19-28
Author(s):  
Alexander A Leung ◽  
Janice L Pasieka ◽  
Martin D Hyrcza ◽  
Danièle Pacaud ◽  
Yuan Dong ◽  
...  
Keyword(s):  
Cohort Study ◽  
Administrative Data ◽  
Laboratory Data ◽  
Population Based ◽  
Incidence Rates ◽  
Primary Objective ◽  
Administrative Databases ◽  
Secondary Objective ◽  
True Frequency ◽  
Clinical Records

Objective Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data. Design Population-based cohort study in Alberta, Canada from 2012 to 2019. Methods Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated. Results A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60–79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algorithm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely approximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year. Conslusion The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

Incidência da utilização de protetores bucais em diversos esportes de contato

2020 ◽  
Vol 12 (45) ◽  
pp. 118-122
Author(s):  
Victor Paes Dias Gonçalves ◽  
Hugo Leonardo Matias Nahmias ◽  
Marcus Menezes Alves Azevedo
Keyword(s):  
Martial Arts ◽  
Rio De Janeiro ◽  
Dental Trauma ◽  
Primary Objective ◽  
Type Ii ◽  
Contact Sports ◽  
The Face ◽  
Secondary Objective ◽  
The City

Among contact sports, the practice of martial arts offers a greater risk of causing dental trauma and fractures as contact with the face is more frequent. The primary objective of the research is to evaluate the incidence of mouthguard use, and the secondary objective is to verify which type has a greater predominance and the difficulties in its use correlating to the type of mouthguard used. A documentary study was carried out with 273 athletes of different contact sports, among them: MMA, Boxing, Muay Thai, Jiu-Jitsu, and Taekwondo of the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. It was concluded that the most commonly used mouthguard is PB Boils and Bites - Type II and its level of approval is poor, interfering with the athletes’ performance, mainly in relation to the breathing factor.

scholarly journals Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 763
Author(s):  
Daniele Roberto Giacobbe ◽  
Chiara Russo ◽  
Veronica Martini ◽  
Silvia Dettori ◽  
Federica Briano ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Bloodstream Infections ◽  
Cross Sectional Study ◽  
Primary Objective ◽  
Sectional Study ◽  
Cross Sectional ◽  
First Line Therapy ◽  
Large Teaching Hospital ◽  
Secondary Objective ◽  
Medical Wards

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.

scholarly journals Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States

2021 ◽  
Author(s):  
Nathaniel J Rhodes ◽  
Atheer Dairem ◽  
William J Moore ◽  
Anooj Shah ◽  
Michael J Postelnick ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Therapy ◽  
Supportive Care ◽  
The United States ◽  
Primary Objective ◽  
Point Prevalence ◽  
Medical Centers ◽  
Academic Medical ◽  
History Of ◽  
Secondary Objective

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. Methods We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19–targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). Results A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19–directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). Conclusion While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

scholarly journals A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors

2021 ◽  
Author(s):  
Noboru Yamamoto ◽  
Toshio Shimizu ◽  
Kan Yonemori ◽  
Shigehisa Kitano ◽  
Shunsuke Kondo ◽  
...  
Keyword(s):  
Liver Function ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Enzyme Inhibitor ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Phase 1 Study ◽  
Open Label Phase

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

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