Plexiform neurofibroma: shedding light on the investigational agents in clinical trials

2021 ◽  
Author(s):  
Simge Acar ◽  
Amy E. Armstrong ◽  
Angela C. Hirbe
Keyword(s):  
Clinical Trials ◽  
Plexiform Neurofibroma ◽  
Investigational Agents

scholarly journals Repurposing Immunomodulatory Therapies against Coronavirus Disease 2019 (COVID-19) in the Era of Cardiac Vigilance: A Systematic Review

2020 ◽  
Vol 9 (9) ◽  
pp. 2935
Author(s):  
Courtney M. Campbell ◽  
Avirup Guha ◽  
Tamanna Haque ◽  
Tomas G. Neilan ◽  
Daniel Addison
Keyword(s):  
Clinical Trials ◽  
Cancer Therapies ◽  
Clinical Safety ◽  
Randomized Evaluation ◽  
Therapeutic Trials ◽  
Inflammatory Phase ◽  
Repurposed Drugs ◽  
Intervention Trials ◽  
Investigational Agents ◽  
Immunomodulatory Therapies

The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation. Trials (n = 226) were fully assessed for the use of a repurposed drug, identifying a total of 141 therapeutic trials using a repurposed drug to target inflammation in COVID-19 infection. Building on the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial demonstrating the benefit of low dose dexamethasone in COVID-19, repurposed drugs targeting inflammation are promising. Repurposed drugs directed at inflammation in COVID-19 primarily have been drawn from cancer therapies and immunomodulatory therapies, specifically targeted anti-inflammatory, anti-complement, and anti-rejection agents. The proposed mechanisms for many cytokine-directed and anti-rejection drugs are focused on evidence of efficacy in cytokine release syndromes in humans or animal models. Anti-complement-based therapies have the potential to decrease both inflammation and microvascular thrombosis. Cancer therapies are hypothesized to decrease vascular permeability and inflammation. Few publications to date describe using these drugs in COVID-19. Early COVID-19 intervention trials have re-emphasized the subtle, but important cardiotoxic sequelae of potential therapies on outcomes. The volume of trials targeting the COVID-19 hyper-inflammatory phase continues to grow rapidly with the evaluation of repurposed drugs and late-stage investigational agents. Leveraging known clinical safety profiles and pharmacodynamics allows swift investigation in clinical trials for a novel indication. Physicians should remain vigilant for cardiotoxicity, often not fully appreciated in small trials or in short time frames.

scholarly journals Remote Delivery of Motor Function Assessment and Training for Clinical Trials in Neuromuscular Disease: A Response to the COVID-19 Global Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Meredith K. James ◽  
Kristy Rose ◽  
Lindsay N. Alfano ◽  
Natalie F. Reash ◽  
Michelle Eagle ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Physical Therapists ◽  
Rapid Development ◽  
Clinical Care ◽  
Neuromuscular Disorders ◽  
Mitigation Strategies ◽  
Study Protocols ◽  
Travel Restrictions ◽  
Clinical Outcome Assessments ◽  
Investigational Agents

Clinical outcome assessments of function or strength, assessed by physical therapists, are commonly used as primary endpoints in clinical trials, natural history studies and within clinics for individuals with neuromuscular disorders. These evaluations not only inform the efficacy of investigational agents in clinical trials, but also importantly track disease trajectory to prospectively advise need for equipment, home and work modifications, and other assistive devices. The COVID-19 pandemic had a global impact on the safety and feasibility of in-person visits and assessments, necessitating rapid development of mitigation strategies to ensure ongoing collection of key clinical trial endpoints and access to expert clinical care despite travel restrictions. Physical therapists who are expert in neuromuscular disorders working across clinics, countries, and clinical trials developed initial guidelines and methods for the suitability and feasibility of performing remote evaluations. A number of Sponsors introduced amendments to their study protocols to enable remote evaluations, supported by live video streaming of the assessment to their local clinical evaluators. Similarly, application of these techniques to clinical telemedicine enabled objective evaluations for use in payer discussions, equipment procurement, and general access to expert physical therapy services. Here we report on our methodology for adapting current practices to remote testing and considerations for remote evaluations.

scholarly journals Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents

2016 ◽  
Vol 23 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Meredith K. Chuk ◽  
Yeruk Mulugeta ◽  
Michelle Roth-Cline ◽  
Nitin Mehrotra ◽  
Gregory H. Reaman
Keyword(s):  
Clinical Trials ◽  
Oncology Clinical Trials ◽  
Investigational Agents

Interest, attitudes, and participation in clinical trials among lymphoma patients with online access

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19514-e19514
Author(s):  
K. Schwartz ◽  
Keyword(s):  
Clinical Trials ◽  
Study Design ◽  
Treatment Decision ◽  
Participation Rates ◽  
Regular Treatment ◽  
Study Enrollment ◽  
Study Protocols ◽  
Survey Results ◽  
Online Access ◽  
Investigational Agents

e19514 Background: There is an increasing number of investigational agents for lymphomas and a limited patient pool, approximately 5% of available patients. Thus, identifying and addressing obstacles to study enrollment is vital to making progress. Methods: This analysis was made from a non-random population of 251 lymphoma patients with online access to our survey. Results: In this cohort, 43% reported High Interest in clinical trials, 50% have Considered Trials, and 27% Have Participated. Patients who considered studies (126) ranked the following reasons for declining as significant: Randomization (70), Insurance (49), Study Risks / Toxicities (42), Travel and Lodging (30), Eligibility (28), Tests and Procedures (12), and a perception that Regular Treatment is superior (6). See Table 1 for associations with consideration of clinical trials and participation. Conclusions: In this cohort, interest in clinical trials and participation rates were much higher than generally cited. As expected, the discussion of clinical trials with the patient's oncologist was associated with the highest consideration (85%) and participation (53%) rates, suggesting a need to increase awareness of study protocols among treating physicians so that this discussion can become more routine. Patient issues and perceptions regarding randomization, study risk, eligibility, and tests and procedures suggest an opportunity to improve enrollment in clinical trials by focusing on these aspects of study design, specifically, attending to the rationale of the protocol as a treatment decision. [Table: see text] No significant financial relationships to disclose.

Radiotherapy for Soft Tissue Sarcoma: 50 Years of Change and Improvement

2014 ◽  
pp. 244-251 ◽  
Author(s):  
Dian Wang ◽  
Ross A. Abrams
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Target Volume ◽  
Image Guided Radiotherapy ◽  
Image Guided ◽  
The Past ◽  
Investigational Agents

Radiotherapy for soft tissue sarcoma (STS) has advanced significantly over the past 50 years. This review focuses briefly on the period from 1964 to 1999 and more substantially on the changes of the past 15 years, such as IMRT and image-guided radiotherapy (IG-RT), especially when brought together (IG-IMRT) in the same planning and delivery process to treat localized STS. In particular, the introduction of IG-RT, target volume definitions for IG-RT, and review of recent clinical trials using IG-RT to treat localized STS in extremity will be reviewed. Finally, potential investigational agents combined with IG-RT to improve outcomes in patients with localized STS are discussed.

Review of Available and Investigational Biologics and Non-Biologic Small Molecules for the Treatment of Plaque Psoriasis

2016 ◽  
Vol 2 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Yasmin Amir ◽  
Mark G. Lebwohl
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Study Design ◽  
Primary Endpoint ◽  
Plaque Psoriasis ◽  
Patient Demographics ◽  
Accurate Comparison ◽  
Investigational Agents

Background In recent years, the number of agents for treatment of plaque psoriasis has increased rapidly. Objective To compare available and investigational agents for treatment of psoriasis. Methods Pivotal clinical trials for infliximab, etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, methotrexate, tofacitinib, and apremilast in plaque psoriasis were identified. Percentages of patients achieving PASI 75, 90, and 100 were extracted. Results Seventeen publications, including data from 21 trials, were reviewed. All medications were more efficacious in achieving PASI 75 compared to placebo. Ixekizumab exhibited the greatest difference in PASI 75 and PASI 90, while brodalumab showed the greatest difference in PASI 100. Limitations Heterogeneity existed in patient demographics and study design including primary endpoint weeks between trials. Data included were only from the primary endpoint week. Conclusions All biologics exhibited greater PASI improvement than placebo, with newer agents more capable of achieving PASI 90 and PASI 100. Head-to-head comparator trials are needed for more accurate comparison.

Adverse event (AE) assessment lists for clinical trials (CTs) influence AE reporting rates: An evaluation of AE data collected on North Central Cancer Treatment Group CTs

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6517-6517
Author(s):  
M. R. Mahoney ◽  
D. J. Sargent ◽  
M. E. Campbell ◽  
B. P. Hobbs ◽  
J. W. Kugler ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Case Report ◽  
Treatment Group ◽  
Prospective Study ◽  
North Central ◽  
Significant Difference ◽  
Investigational Agents ◽  
A Prospective Study ◽  
Reporting Rates

6517 Background: In NCCTG CTs a subset of AEs are assessed at each patient (pt) evaluation based on the known safety profile of agents(s). The NCCTG routinely pre-fills the “known” AE list onto CT Case Report Forms (CRFs). Newly identified AEs may expand the AE assessment list for ongoing CTs. Our survey of NCCTG AE data (JCO 2005), demonstrated that 85% of AEs reported were pre-filled on CRFs, of which, 83% did not actually occur (Grade 0). Extending this work, we evaluated the influence of pre-filling AEs on CRFs, relative to the final AE rates reported. Methods: Our non-random sample contains 507,899 AEs collected from 1/99–6/06 on 74 NCCTG CTs, 13 of which had AEs added to the CRF pre-fill list during the CT (2,604 pts, 3 Ph I/II, 8 Ph II, 2 Ph III, 9 investigational agents). Results: An average of 2.8 AEs (range 1–6) were added to CRFs for ongoing CTs, primarily for Oxaliplatin induced AEs. 58% (21/36) of AEs added during a CT were not reported prior to the addition, 22% (8) were not reported afterwards. 5 CTs had significantly higher AE rates (p<0.01) after expanding the AE list, most notably for required blood chemistries (SGOT/alk phos/creatinine/bilirubin 14.2 vs 0.72%). Overall, the same AEs were 4-fold (range 0–25) as likely to be reported when pre-filled on the CRF. Regardless of pre-filling, only 6% of the newly required AEs were Gr 3+. Conclusions: Our data suggest a significant difference between the AE rates reported if included in the CT CRF assessment list. This may significantly influence the reported results of a CT, explaining differential AE rates reported across CTs of the same agent(s). A prospective study is planned to formally evaluate this observation. Supported by NIH Grant CA25224. No significant financial relationships to disclose.

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