Evidence map›Paper›PMID 33027815›Full record

Trial reportNeurosurgery2021

A Phase II and Pharmacodynamic Trial of RO4929097 for Patients With Recurrent/Progressive Glioblastoma.

David M Peereboom, Xiaobu Ye, Tom Mikkelsen, Glenn J Lesser, Frank S Lieberman, H Ian Robins, Manmeet S Ahluwalia, Andrew E Sloan, Stuart A Grossman

Open access · greenAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurosurgery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.2field-weighted citation impact, top 11% 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.

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

24 citing papers in PubMed, 33 citations in OpenAlex.

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  19. Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 8 institutions in 1 country.

David M PeereboomBurkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, Ohio.
Xiaobu YeDepartment of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
Tom MikkelsenDepartment of Neurosurgery, Henry Ford Hospital, Detroit, Michigan.
Glenn J LesserHematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina.
Frank S LiebermanDepartment of Neurology, Hillman Cancer Center of University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
H Ian RobinsDepartment of Human Oncology, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
Manmeet S AhluwaliaBurkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, Ohio.
Andrew E SloanDepartment of Neurological Surgery, Seidman Cancer Center, University Hospitals & Case Comprehensive Cancer Center, Cleveland, Ohio.
Stuart A GrossmanThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cleveland Clinic · USCase Comprehensive Cancer CenterHenry Ford Hospital · USJohns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USUniversity of Wisconsin Carbone Cancer Center · USUPMC Hillman Cancer Center · USWake Forest University · US

Funding

Adult Brain Tumor Consortium (ABTC)UM1CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A · 2014 to 2020
$9.7M
NCI NIH HHS UM1 CA137443
6 · The paper itself

Abstract

backgroundCancer stem-like cells are a major cause of resistance to therapy in patients with glioblastoma (GBM) as well as other cancers. Tumor cells are maintained in a stem-like proliferative state in large part through the Notch signaling pathway. The function of this pathway in turn depends on gamma secretase activity. Inhibition of this enzyme therefore inhibits the Notch pathway and tumor growth as measured by a reduction in the formation of brain tumor neurospheres in murine models. RO4929097 is an oral gamma secretase inhibitor.

objectiveTo estimate the 6-mo progression-free survival rate (PFS6) in patients with progressive GBM and to inhibit by 50% the generation of neurospheres in fresh tissue resected from patients treated with RO4929097.

methodsIn this phase II and pharmacodynamic study, patients with recurrent GBM received RO4929097 in a study of 2 groups. Group A patients had unresectable disease and received drug in a standard phase II design. Group B patients had resectable disease and received drug before and after surgical resection. Endpoints included PFS6 and the inhibition of neurosphere formation in the resected tumor samples.

resultsA total of 47 patients received treatment, 7 of whom had tumor resection. The PFS6 was 4%, and the inhibition of neurosphere formation occurred in 1 of 7 patient samples.

conclusionRO4929097 was inactive in recurrent GBM patients and demonstrated minimal inhibition of neurosphere formation in fresh tissue samples.

Indexed as

AdultAgedBenzazepinesBrain NeoplasmsFemaleFluorenesFluorocarbonsGlioblastomaHumansKetonesMiddle AgedNeoplasm Recurrence, LocalNeoplastic Stem CellsProgression-Free Survival2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamideBenzazepinesFluorenesFluorocarbonsKetonesGamma secretaseNotchPharmacodynamicPhase 2Recurrent glioblastomaRO4929097Stem cell

Identifiers

PMID33027815
PMCPMC7919338
OpenAlexW3092429576

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.