Evidence map›Paper›PMID 41991689›Full record

Trial reportNature medicine2026

Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial.

Patrick J Grohar, Rachel Heise, Mary Frances Wedekind, Karla Ballman, Leo Mascarenhas, Steven G DuBois, Robert G Maki, Elissa A Boguslawski, Jenna M Gedminas, Elizabeth R Wilson and 26 more

Abstract readClinical Trial, Phase IIClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Patrick J GroharDivision of Pediatric Hematology/Oncology, University of Michigan Medical School, C.S. Mott Children's Hospital, Rogel Cancer Center, Ann Arbor, MI, USA. grohar@med.umich.edu.ORCID http://orcid.org/0000-0002-1071-4563
Rachel HeiseWeill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7785-4579
Mary Frances WedekindPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Karla BallmanMayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4492-0357
Leo MascarenhasGuerin Children's and Cedars Sinai Cancer, Cedars Sinai Health Sciences University, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7790-0777
Steven G DuBoisDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.
Robert G MakiMemorial Sloan-Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9853-2528
Elissa A BoguslawskiDivision of Pediatric Hematology/Oncology, University of Michigan Medical School, C.S. Mott Children's Hospital, Rogel Cancer Center, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-4233-903X
Jenna M GedminasDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
Elizabeth R WilsonDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Elaine ThomasPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Blair SegersDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Lea F SurreyDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6944-2232
Cora RickerDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1202-5603
Kelly KlegaDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.
Fariba NavidCancer and Blood Disease Institute, Children's Hospital of Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Gretchen Y LamDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0009-0005-5852-8865
Stephanie TheDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Rebecca KaufmanDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8535-9730
Ryan D RobertsDepartment of Pediatrics, Center for Childhood Cancer, Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA.
Masanori HayashiDepartment of Pediatrics, University of Colorado Anschutz Medical Campus and Center for Cancer and Blood Disorders, Children's Hospital of Colorado, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-9508-0159
Esther MenaMolecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lindsey OvermanSarcoma Alliance for Research through Collaboration, Ann Arbor, MI, USA.ORCID http://orcid.org/0009-0008-6454-3035
Cody PeerClinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Keith SchmidtClinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Mark S DiamondDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
William D FiggClinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2428-5613
Rochelle BagatellDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
M Liza LindenbergMolecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Peter L ChoykeMolecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1086-8826
Brian D CromptonDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9404-6621
Brigitte C WidemannPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9198-7175
John W GlodPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Theodore W LaetschDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8497-3138
Denise K ReinkeUniversity of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8662-7060
Rashmi ChughUniversity of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Pediatric Oncology Branch Clinical Care and EducationZIEBC011516 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GLOD, JOHN · 2013 to 2025
$69.1M
Growth Factor Imaging and PhotoimmunotherapyZIABC010656 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CHOYKE, PETER L · 2009 to 2024
$31.6M
Using Clinical Pharmacology Principles to Develop New Anticancer TherapiesZICSC006537 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$14.4M
PROJECT 3: Applying Liquid Biopsy Technologies to Detect Clinical Response and Mechanisms of Resistance in the Treatment of LMSP50CA272170 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JUDY E. GARBER · 2022 to 2026
$13.3M
Development of Trabectedin Analogs that Target the EWS-FLI1 Transcription FactorR01CA188314 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI GROHAR, PATRICK J · 2015 to 2019
$2.0M
A collaborative approach to analyze and target the EWS-FLI1 transcription factor in patients with Ewing sarcomaU01CA236220 · NCI · SARC · PI GROHAR, PATRICK J · 2019 to 2023
$2.0M
The interface of transcription, DNA damage and epigenetics: A therapeutic vulnerability of the EWS-FLI1 transcription factorR01CA283058 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Patrick J Grohar · 2023 to 2026
$1.8M
Alex's Lemonade Stand Foundation for Childhood Cancer (Alex's Lemonade Stand Foundation) Center of ExcellenceNCI NIH HHS P30 CA008748NCI NIH HHS P50 CA272170NCI NIH HHS R01 CA188314NCI NIH HHS R01 CA283058NCI NIH HHS U01 CA236220U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA188314U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01CA236220U.S. Department of Health & Human Services | National Institutes of Health (NIH) ZIA BC 010656U.S. Department of Health & Human Services | National Institutes of Health (NIH) ZIC SC 006537U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) ZIE BC 011516
6 · The paper itself

Abstract

Ewing sarcoma (ES) is a bone and soft tissue sarcoma that is absolutely dependent on the EWS::FLI1 transcription factor for cell survival. No compound has been shown to reverse EWS::FLI1 activity in patients, and outcomes for relapsed patients remain poor. Trabectedin above a threshold concentration reverses the activity of EWS::FLI1 and is potentiated by low-dose irinotecan in vivo. This open-label phase 1/2 trial of trabectedin with irinotecan (SARC037) enrolled 37 relapsed/refractory patients with ES. The primary objectives were to determine the safety, tolerability, recommended phase 2 dose (RP2D; phase 1) and objective response rate (ORR; phase 2) of trabectedin administered as a 1-hour infusion in combination with low-dose irinotecan in patients with ES. The secondary objectives were to determine the progression-free survival (PFS), 6-month PFS, duration of response and

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsIrinotecanOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingTrabectedinAdolescentAdultFemaleHumansMaleMiddle AgedYoung AdultEWS-FLI fusion proteinIrinotecanOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSTrabectedin

Identifiers

PMID41991689
PMCPMC13321597

What OpenQuestion holds

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Registered trials

None linked

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.