FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2811343828> ?p ?o ?g. }

• W2811343828 endingPage "913" @default.
• W2811343828 startingPage "913" @default.
• W2811343828 abstract "<h3>Importance</h3> There are no medical interventions for the orphan disease CYLD cutaneous syndrome (CCS). Transcriptomic profiling of CCS skin tumors previously highlighted tropomyosin receptor kinases (TRKs) as candidate therapeutic targets. <h3>Objective</h3> To investigate if topical targeting of TRK with an existing topical TRK inhibitor, pegcantratinib, 0.5% (wt/wt), is safe and efficacious in CCS. <h3>Design, Setting, and Participants</h3> A phase 1b open-label safety study, followed by a phase 2a within-patient randomized (by tumor), double-blind, placebo-controlled trial (the Tropomyosin Receptor Antagonism in Cylindromatosis [TRAC] trial). The setting was a single-center trial based at a tertiary dermatogenetics referral center for CCS (Royal Victoria Infirmary, Newcastle, United Kingdom). Patients who had germline mutations in<i>CYLD</i>or who satisfied clinical diagnostic criteria for CCS were recruited between March 1, 2015, and July 1, 2016. <h3>Interventions</h3> In phase 1b, patients with CCS applied pegcantratinib for 4 weeks to a single skin tumor. In phase 2a, allocation of tumors was to either receive active treatment on the right side and placebo on the left side (arm A) or active treatment on the left side and placebo on the right side (arm B). Patients were eligible if they had 10 small skin tumors, with 5 matched lesions on each body side; patients were randomized to receive active treatment (pegcantratinib) to one body side and placebo to the other side once daily for 12 weeks. <h3>Main Outcomes and Measures</h3> The primary outcome measure was the number of tumors meeting the criteria for response in a prespecified critical number of pegcantratinib-treated tumors. Secondary clinical outcome measures included an assessment for safety of application, pain in early tumors, and compliance with the trial protocol. <h3>Results</h3> In phase 1b, 8 female patients with a median age of 60 years (age range, 41-80 years) were recruited and completed the study. None of the participants experienced any adverse treatment site reactions. Three patients reported reduced pain in treated tumors. In phase 2a (15 patients [13 female; median age, 51 years], with 150 tumors), 2 tumors treated with pegcantratinib achieved the primary outcome measure of response compared with 6 tumors treated with placebo. The primary prespecified number of responses was not met. The incidence of adverse events was low. <h3>Conclusions and Relevance</h3> In this study, pegcantratinib, 0.5% (wt/wt), applied once daily appeared to be well tolerated and to penetrate the tumor tissue; however, the low tumor drug concentrations demonstrated are likely to account for the lack of response. Dose-escalation studies to assess the maximal tolerated dose may be beneficial in future studies of CCS. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN75715723" @default.
• W2811343828 created "2018-07-10" @default.
• W2811343828 creator A5004173654 @default.
• W2811343828 creator A5012435189 @default.
• W2811343828 creator A5018477298 @default.
• W2811343828 creator A5020692726 @default.
• W2811343828 creator A5023057149 @default.
• W2811343828 creator A5029949140 @default.
• W2811343828 creator A5043919062 @default.
• W2811343828 creator A5044488716 @default.
• W2811343828 creator A5046012874 @default.
• W2811343828 creator A5048419838 @default.
• W2811343828 creator A5054905039 @default.
• W2811343828 creator A5056581326 @default.
• W2811343828 creator A5058973407 @default.
• W2811343828 creator A5062338155 @default.
• W2811343828 creator A5064276834 @default.
• W2811343828 creator A5066218486 @default.
• W2811343828 creator A5080531356 @default.
• W2811343828 creator A5091131903 @default.
• W2811343828 date "2018-08-01" @default.
• W2811343828 modified "2023-10-11" @default.
• W2811343828 title "Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib" @default.
• W2811343828 cites W1988921793 @default.
• W2811343828 cites W2093659327 @default.
• W2811343828 cites W2096991001 @default.
• W2811343828 cites W2100426249 @default.
• W2811343828 cites W2120113475 @default.
• W2811343828 cites W2128160112 @default.
• W2811343828 cites W2129208345 @default.
• W2811343828 cites W2130348198 @default.
• W2811343828 cites W2132049244 @default.
• W2811343828 cites W2148776605 @default.
• W2811343828 cites W2152932493 @default.
• W2811343828 cites W2194998434 @default.
• W2811343828 cites W2335155752 @default.
• W2811343828 cites W2473786944 @default.
• W2811343828 cites W2594234238 @default.
• W2811343828 cites W2790254562 @default.
• W2811343828 cites W4236548038 @default.
• W2811343828 cites W4243016105 @default.
• W2811343828 cites W4249999102 @default.
• W2811343828 doi "https://doi.org/10.1001/jamadermatol.2018.1610" @default.
• W2811343828 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6128505" @default.
• W2811343828 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29955768" @default.
• W2811343828 hasPublicationYear "2018" @default.
• W2811343828 type Work @default.
• W2811343828 sameAs 2811343828 @default.
• W2811343828 citedByCount "14" @default.
• W2811343828 countsByYear W28113438282019 @default.
• W2811343828 countsByYear W28113438282020 @default.
• W2811343828 countsByYear W28113438282021 @default.
• W2811343828 countsByYear W28113438282022 @default.
• W2811343828 crossrefType "journal-article" @default.
• W2811343828 hasAuthorship W2811343828A5004173654 @default.
• W2811343828 hasAuthorship W2811343828A5012435189 @default.
• W2811343828 hasAuthorship W2811343828A5018477298 @default.
• W2811343828 hasAuthorship W2811343828A5020692726 @default.
• W2811343828 hasAuthorship W2811343828A5023057149 @default.
• W2811343828 hasAuthorship W2811343828A5029949140 @default.
• W2811343828 hasAuthorship W2811343828A5043919062 @default.
• W2811343828 hasAuthorship W2811343828A5044488716 @default.
• W2811343828 hasAuthorship W2811343828A5046012874 @default.
• W2811343828 hasAuthorship W2811343828A5048419838 @default.
• W2811343828 hasAuthorship W2811343828A5054905039 @default.
• W2811343828 hasAuthorship W2811343828A5056581326 @default.
• W2811343828 hasAuthorship W2811343828A5058973407 @default.
• W2811343828 hasAuthorship W2811343828A5062338155 @default.
• W2811343828 hasAuthorship W2811343828A5064276834 @default.
• W2811343828 hasAuthorship W2811343828A5066218486 @default.
• W2811343828 hasAuthorship W2811343828A5080531356 @default.
• W2811343828 hasAuthorship W2811343828A5091131903 @default.
• W2811343828 hasBestOaLocation W28113438281 @default.
• W2811343828 hasConcept C126322002 @default.
• W2811343828 hasConcept C134139212 @default.
• W2811343828 hasConcept C141071460 @default.
• W2811343828 hasConcept C142724271 @default.
• W2811343828 hasConcept C143998085 @default.
• W2811343828 hasConcept C168563851 @default.
• W2811343828 hasConcept C170493617 @default.
• W2811343828 hasConcept C204787440 @default.
• W2811343828 hasConcept C27081682 @default.
• W2811343828 hasConcept C71924100 @default.
• W2811343828 hasConcept C92020748 @default.
• W2811343828 hasConceptScore W2811343828C126322002 @default.
• W2811343828 hasConceptScore W2811343828C134139212 @default.
• W2811343828 hasConceptScore W2811343828C141071460 @default.
• W2811343828 hasConceptScore W2811343828C142724271 @default.
• W2811343828 hasConceptScore W2811343828C143998085 @default.
• W2811343828 hasConceptScore W2811343828C168563851 @default.
• W2811343828 hasConceptScore W2811343828C170493617 @default.
• W2811343828 hasConceptScore W2811343828C204787440 @default.
• W2811343828 hasConceptScore W2811343828C27081682 @default.
• W2811343828 hasConceptScore W2811343828C71924100 @default.
• W2811343828 hasConceptScore W2811343828C92020748 @default.
• W2811343828 hasIssue "8" @default.
• W2811343828 hasLocation W28113438281 @default.
• W2811343828 hasLocation W28113438282 @default.

• next