Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma
Introduction All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on the...
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BMJ Publishing Group
2025-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/2/e087922.full |
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| author | Marshall Pitz Eng-Siew Koh Elizabeth H Barnes Lucille Sebastian Mandy L Ballinger David M Thomas Christopher O'Callaghan John Simes Hui K Gan Sonia Yip Hao-Wen Sim Desma Spyridopoulos Richard De Abreu Lourenco Cynthia Hawkins Kristen McParland Benjamin Kong Subotheni Thavaneswaran Patrick J Wheeler |
| author_facet | Marshall Pitz Eng-Siew Koh Elizabeth H Barnes Lucille Sebastian Mandy L Ballinger David M Thomas Christopher O'Callaghan John Simes Hui K Gan Sonia Yip Hao-Wen Sim Desma Spyridopoulos Richard De Abreu Lourenco Cynthia Hawkins Kristen McParland Benjamin Kong Subotheni Thavaneswaran Patrick J Wheeler |
| author_sort | Marshall Pitz |
| collection | DOAJ |
| description | Introduction All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on their molecular profile, maximising the chances of patient benefit while simultaneously testing multiple novel drugs.Methods and analysis Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2) will be an international, phase 2, multicentre, open-label, biomarker-directed, umbrella clinical trial for recurrent isocitrate dehydrogenase mutant, histologically grade 2/3 gliomas. Investigational treatment will be assigned based on molecular profiling of contemporaneous tissue obtained at disease relapse using next-generation sequencing. LUMOS-2 will begin with three therapeutic treatment arms: paxalisib, cadonilimab and selinexor. Patient molecular profiles will be assessed by an expert, multidisciplinary Molecular Tumour Advisory Panel. Patients whose molecular profile is considered suitable for a targeted agent like paxalisib will be allocated to that arm, others will be randomised to the available arms of the trial. The primary endpoint is progression-free survival at 6 months. Secondary objectives include assessment of overall survival, response rate, safety and quality of life measures. Two additional therapeutic arms are currently in development.Ethics and dissemination Central ethics approval was obtained from the Sydney Local Health District Ethics Review Committee, Royal Prince Alfred Hospital Zone, Sydney, Australia (Approval: 2022/ETH02230). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. A report describing the results of the study will be submitted to international meetings and peer-reviewed journals.Trial registration number ACTRN12623000096651. |
| format | Article |
| id | doaj-art-ba365959f64549ce8c2810810c29232d |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-ba365959f64549ce8c2810810c29232d2025-02-11T09:50:13ZengBMJ Publishing GroupBMJ Open2044-60552025-02-0115210.1136/bmjopen-2024-087922Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 gliomaMarshall Pitz0Eng-Siew Koh1Elizabeth H Barnes2Lucille Sebastian3Mandy L Ballinger4David M Thomas5Christopher O'Callaghan6John Simes7Hui K Gan8Sonia Yip9Hao-Wen Sim10Desma Spyridopoulos11Richard De Abreu Lourenco12Cynthia Hawkins13Kristen McParland14Benjamin Kong15Subotheni Thavaneswaran16Patrick J Wheeler17University of Manitoba, Winnipeg, Manitoba, CanadaRadiation Oncology, Liverpool Cancer Therapy Centre, Liverpool, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaOmico, Australian Genomic Cancer Medicine Centre, Sydney, New South Wales, AustraliaOmico, Australian Genomic Cancer Medicine Centre, Sydney, New South Wales, AustraliaOmico, Australian Genomic Cancer Medicine Centre, Sydney, New South Wales, AustraliaCanadian Cancer Trials Group, Queen`s University, Kingston, Ontario, CanadaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaMedical Oncology, Olivia Newton-John Cancer Centre, Heidelberg, Victoria, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaCentre for Health Economics Research and Evaluation, University of Technology Sydney, Broadway, New South Wales, AustraliaDivision of Hematology/Oncology, The Hospital for Sick Children, Institute of Medical Sciences, The University of Toronto, Toronto, Ontario, CanadaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaThe NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, AustraliaIntroduction All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on their molecular profile, maximising the chances of patient benefit while simultaneously testing multiple novel drugs.Methods and analysis Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2) will be an international, phase 2, multicentre, open-label, biomarker-directed, umbrella clinical trial for recurrent isocitrate dehydrogenase mutant, histologically grade 2/3 gliomas. Investigational treatment will be assigned based on molecular profiling of contemporaneous tissue obtained at disease relapse using next-generation sequencing. LUMOS-2 will begin with three therapeutic treatment arms: paxalisib, cadonilimab and selinexor. Patient molecular profiles will be assessed by an expert, multidisciplinary Molecular Tumour Advisory Panel. Patients whose molecular profile is considered suitable for a targeted agent like paxalisib will be allocated to that arm, others will be randomised to the available arms of the trial. The primary endpoint is progression-free survival at 6 months. Secondary objectives include assessment of overall survival, response rate, safety and quality of life measures. Two additional therapeutic arms are currently in development.Ethics and dissemination Central ethics approval was obtained from the Sydney Local Health District Ethics Review Committee, Royal Prince Alfred Hospital Zone, Sydney, Australia (Approval: 2022/ETH02230). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. A report describing the results of the study will be submitted to international meetings and peer-reviewed journals.Trial registration number ACTRN12623000096651.https://bmjopen.bmj.com/content/15/2/e087922.full |
| spellingShingle | Marshall Pitz Eng-Siew Koh Elizabeth H Barnes Lucille Sebastian Mandy L Ballinger David M Thomas Christopher O'Callaghan John Simes Hui K Gan Sonia Yip Hao-Wen Sim Desma Spyridopoulos Richard De Abreu Lourenco Cynthia Hawkins Kristen McParland Benjamin Kong Subotheni Thavaneswaran Patrick J Wheeler Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma BMJ Open |
| title | Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma |
| title_full | Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma |
| title_fullStr | Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma |
| title_full_unstemmed | Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma |
| title_short | Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma |
| title_sort | low anaplastic grade glioma umbrella study of molecular guided therapies lumos 2 study protocol for a phase 2 prospective multicentre open label multiarm biomarker directed signal seeking umbrella clinical trial for recurrent idh mutant grade 2 3 glioma |
| url | https://bmjopen.bmj.com/content/15/2/e087922.full |
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