Evidence map›Paper›PMID 32187457›Full record

Trial reportThe New England journal of medicine2020

Selumetinib in Children with Inoperable Plexiform Neurofibromas.

Andrea M Gross, Pamela L Wolters, Eva Dombi, Andrea Baldwin, Patricia Whitcomb, Michael J Fisher, Brian Weiss, AeRang Kim, Miriam Bornhorst, Amish C Shah and 19 more

Erratum issued 6 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 6 registered trials, which are not on this map. Cited by 430 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
430citing papers in PubMed, 5 pooled it
33.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01362803 phase1 / phase2active not recruitingnot on this map

A Phase I/II Study of the Mitogen Activated Protein Kinase (MEK) 1 Inhibitor Selumetinib (AZD6244; Hydrogen Sulfate in Children With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN)

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2011 to 2032Enrolled99ConditionsNeurofibromatosis 1, Neurofibromatosis Type 1, NF1, Neurofibroma, PlexiformArmsAZD6244
NCT05238909 enrolling by invitationnot on this mapstarted 2022, after this paper: background citation

Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden

Typeobservational_patient_registrySponsorAnn & Robert H Lurie Children's Hospital of ChicagoRan2022 to 2027Enrolled200ConditionsNeurofibromatosis 1, NF1, Neurofibromatosis Type 1
NCT06490757 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

A Phase 2 Open-label Single-arm Trial of JAK1 Inhibitor for the Treatment of Large Inflammatory Hepatocellular Adenomas

TypeinterventionalSponsorAssistance Publique - Hôpitaux de ParisRan2024 to 2028Enrolled25ConditionsInflammatory Hepatocellular AdenomaArmsBaricitinib
NCT06620354 phase2not yet recruitingnot on this mapstarted 2024, after this paper: background citation

Prospective, One-arm, Phase II Clinical Study of Smeitinib Hydrosulfate Capsules for the Treatment of Patients With Type I Neurofibromatosis

TypeinterventionalSponsorSun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRan2024 to 2026Enrolled33ConditionsNeurofibromatosis 1ArmsSelumetinib
NCT06621082 phase2not yet recruitingnot on this mapstarted 2024, after this paper: background citation

A Prospective, One-arm, Phase II Clinical Study of Smeitinib Hydrosulfate Capsules for the Treatment of Patients With Type I Neurofibromatosis After Surgery

TypeinterventionalSponsorSun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRan2024 to 2026Enrolled19ConditionsNeurofibromatosis 1ArmsSelumetinib
NCT06763315 phase2not yet recruitingnot on this mapstarted 2025, after this paper: background citation

The Efficacy, Safety, and Long-Term Prognosis of Low-Dose Selumetinib in the Treatment of Neurofibromatosis Type 1 Associated Plexiform Neurofibromas in Chinese Children: a Multicenter Randomized Controlled Trial

TypeinterventionalSponsorWest China HospitalRan2025 to 2028Enrolled50ConditionsPlexiform Neurofibromas (PN)ArmsSelumetinib
3 · Its place in the literature

Who cites it

430 citing papers in PubMed, 5 syntheses or guidelines pooled it, 667 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. [Clarification the terms and definitions related to neurofibromatosis type 1].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024
    Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. SARC031: A Phase II Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  10. Trial
  11. Trial
  12. Trial
  13. ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Trial
  14. Trial
  15. Trial
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  20. Review

370 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 6 institutions in 2 countries.

Andrea M GrossFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Pamela L WoltersFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Eva DombiFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Andrea BaldwinFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Patricia WhitcombFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Michael J FisherFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Brian WeissFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
AeRang KimFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Miriam BornhorstFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Amish C ShahFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Staci MartinFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Marie C RoderickFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Dominique C PichardFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Amanda CarbonellFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Scott M PaulFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Janet TherrienFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Oxana KapustinaFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Kara HeiseyFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
D Wade ClappFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Chi ZhangFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Cody J PeerFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
William D FiggFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).ORCID 0000-0003-2428-5613
Malcolm SmithFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
John GlodFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Jaishri O BlakeleyFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Seth M SteinbergFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
David J VenzonFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
L Austin DoyleFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Brigitte C WidemannFrom the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Cancer Institute (WIA) · INFrederick National Laboratory for Cancer Research · USNational Institutes of Health · USChildren's Hospital of Philadelphia · USChildren's National · USCincinnati Children's Hospital Medical Center · US

Funding

Pediatric Oncology Branch Clinical Care and EducationZIEBC011516 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GLOD, JOHN · 2013 to 2025
$69.1M
Project 4: Secondary Cancers Among NF1 Cancer SurvivorsU54CA196519 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI Yunlong Liu · 2015 to 2026
$26.9M
Sample Processing and Analytical Methods Development for New Anticancer AgentsZICSC006536 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$18.1M
Pediatric Oncology Branch Behvioral Science CoreZIDBC011517 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GLOD, JOHN · 2013 to 2025
$15.6M
Office of Collaborative BiostatisticsZIDSC007202 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI CHOO-WOSOBA, HYOYOUNG · 2009 to 2025
$14.5M
Using Clinical Pharmacology Principles to Develop New Anticancer TherapiesZICSC006537 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$14.4M
Therapy for NF1-Related Tumors and other Genetic Tumor Predisposition SyndromesZIABC010801 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WIDEMANN, BRIGITTE · 2009 to 2020
$13.8M
Intramural NIH HHS Z99 CA999999NCI NIH HHS U54 CA196519United States U54 CA196519-04
6 · The paper itself

Abstract

backgroundNo approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.

methodsWe conducted an open-label, phase 2 trial of selumetinib to determine the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit. Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain, quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable).

resultsA total of 50 children (median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain (26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in child-reported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia.

conclusionsIn this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. (Funded by the Intramural Research Program of the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803.).

Indexed as

AdolescentBenzimidazolesChildChild, PreschoolFemaleHumansMaleMitogen-Activated Protein Kinase KinasesNauseaNeurofibroma, PlexiformNeurofibromatosis 1PainPatient Reported Outcome MeasuresProgression-Free SurvivalProtein Kinase InhibitorsTumor BurdenAZD 6244BenzimidazolesMitogen-Activated Protein Kinase KinasesProtein Kinase Inhibitors

Identifiers

PMID32187457
PMCPMC7305659
OpenAlexW3010907970

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.