Evidence map›Paper›PMID 38124481›Full record

ArticleNeuro-oncology2024

Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.

Sabine Mueller, Cassie Kline, Andrea Franson, Jasper van der Lugt, Michael Prados, Sebastian M Waszak, Sabine L A Plasschaert, Annette M Molinaro, Carl Koschmann, Javad Nazarian

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05009992 (A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 25% 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.

NCT05009992 phase2recruitingnot on this map

A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas (DMGs) Including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression

TypeinterventionalSponsorUniversity of California, San FranciscoRan2021 to 2029Enrolled360ConditionsDiffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Diffuse Midline Glioma, H3 K27M-MutantArmsONC201, Radiation Therapy, Paxalisib, DNX-2401
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
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

10 authors at 5 institutions in 3 countries.

Sabine MuellerDepartment of Neurology, Neurosurgery and Pediatrics, University of California, San Francisco, California, USA.ORCID 0000-0002-3452-5150
Cassie KlineDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Andrea FransonDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Jasper van der LugtPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Michael PradosDepartment of Neurosurgery and Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Sebastian M WaszakDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Sabine L A PlasschaertPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Annette M MolinaroDivision of Biomedical Statistics and Informatics, Department of Neurosurgery, University of California, San Francisco, San Francisco, California, USA.
Carl KoschmannDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Javad NazarianResearch Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.
University of California, San Francisco · USPrincess Máxima Center · NLUniversity of Michigan · USChildren's Hospital of Philadelphia · USChildren's National · US

Funding

Targeting EGFR/FOXG1-mediated resistance to ONC201 in H3K27M-mutant diffuse midline gliomaR01NS124607 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carl J Koschmann · 2022 to 2026
$2.2M
The role of ATRX mutation in the epigenetic dysregulation of cell cycle in pediatric high-grade gliomaR01NS119231 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2021 to 2025
$1.9M
NINDS NIH HHS R01 NS119231NINDS NIH HHS R01 NS124607NINDS NIH HHS R01-NS124607
6 · The paper itself

Abstract

Background Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. Methods We have previously shown preclinical efficacy of targeting both oxidative phosphorylation and glycolysis through treatment with ONC201, which activates the mitochondrial protease ClpP, and paxalisib, which inhibits PI3K/mTOR, respectively. Results ONC201 and paxalisib combination treatment aimed at inducing metabolic distress led to the design of the first DMG-specific platform trial PNOC022 (NCT05009992). Conclusions Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG.

Indexed as

Brain NeoplasmsGliomaAdaptive Clinical Trials as TopicAdolescentAdultAntineoplastic Combined Chemotherapy ProtocolsChildFemaleHumansMalePrognosisPyrimidinesQuality of LifeResearch DesignYoung AdultPyrimidinesclinical trialsdiffuse midline gliomaONC201paxalisibpediatric neuro-oncology

Identifiers

PMID38124481
PMCPMC11066905
OpenAlexW4390066251

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.