Evidence map›Paper›PMID 34301221›Full record

Trial reportBMC cancer2021

A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma.

Stephen W Booth, Toby A Eyre, John Whittaker, Leticia Campo, Lai Mun Wang, Elizabeth Soilleux, Daniel Royston, Gabrielle Rees, Murali Kesavan, Catherine Hildyard and 5 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01977638 (Phase 1 Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CXD101 Given Orally), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 31% 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.

NCT01977638 phase1completednot on this map

Phase 1 Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CXD101 Given Orally (Twice Daily Dosing for 5 Consecutive Days in a 21-day Period) in Patients With Advanced Malignancies Expressing the Biomarker HR23B

TypeinterventionalSponsorOxford University Hospitals NHS TrustRan2014 to 2022Enrolled51ConditionsAdvanced CancerArmsCXD101
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
  3. Article
  4. 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

15 authors at 4 institutions in 1 country.

Stephen W BoothDepartment of Haematology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, UK. stephen.booth@nhs.net.ORCID http://orcid.org/0000-0003-2687-0234
Toby A EyreDepartment of Haematology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, UK.
John WhittakerCelleron Therapeutics Ltd, Oxford, UK.
Leticia CampoDepartment of Oncology, University of Oxford, Oxford, UK.
Lai Mun WangDepartment of Cellular Pathology, Oxford University Hospitals, Oxford, UK.
Elizabeth SoilleuxDepartment of Pathology, University of Cambridge, Cambridge, UK.
Daniel RoystonDepartment of Cellular Pathology, Oxford University Hospitals, Oxford, UK.
Gabrielle ReesDepartment of Cellular Pathology, Oxford University Hospitals, Oxford, UK.
Murali KesavanDepartment of Haematology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, UK.
Catherine HildyardDepartment of Haematology, Milton Keynes University Hospital, Milton Keynes, UK.
Farasat KazmiDepartment of Oncology, University of Oxford, Oxford, UK.
Nick La ThangueCelleron Therapeutics Ltd, Oxford, UK.
David KerrCelleron Therapeutics Ltd, Oxford, UK.
Mark R MiddletonDepartment of Oncology, University of Oxford, Oxford, UK.
Graham P CollinsDepartment of Haematology, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, UK.
University of Oxford · GBOxford University Hospitals NHS Trust · GBMilton Keynes Hospital · GBUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity.

methodsPatients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils < 1.5 × 10

resultsFifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3-4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2-5.4) in solid-organ cancers and 2.6 months (95%CI 1.2-5.6) in lymphomas. HR23B status did not predict response.

conclusionsCXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted.

trial registrationClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013.

Indexed as

AdultAgedBiomarkers, TumorDNA-Binding ProteinsDNA Repair EnzymesFemaleGene ExpressionHistone Deacetylase InhibitorsHumansImmunohistochemistryLymphomaMaleMiddle AgedNeoplasmsNeoplasm StagingTreatment OutcomeBiomarkers, TumorDNA-Binding ProteinsDNA Repair EnzymesHistone Deacetylase InhibitorsRAD23B protein, humanBiomarkerHistone deacetylase (HDAC)HR23BLymphoma

Identifiers

PMID34301221
PMCPMC8306282
OpenAlexW3186753291

What OpenQuestion holds

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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.