First Progression of GlioblastomaPhase 3LEGATONCT05904119
Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study
A Phase 3 study testing Lomustine and Reirradiation in people with First Progression of Glioblastoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 45 sites in 11 countries.
Trial summary
Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- First Progression of Glioblastoma
- What is being tested?
- Lomustine and Reirradiation
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 411 participants
- Where
- 45 sitesin 11 countries
- Study dates
- 15 Mar 2024to Feb 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Before patient's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.
- Patients with first progression or recurrent glioblastoma after standard chemoradiotherapy (any treatment other than use of nitroureas) having occurred at least 6 months after the end of prior radiotherapy
- Measurable disease according to RANO criteria with a maximum tumour diameter of 5 cm (local investigator assessment)
- In case of surgery for recurrence: fully recovered from surgery, confirmation of recurrence by histology, and patient fit for treatment as per local investigator assessment.
- Histologically proven diagnosis of glioblastoma, IDH wildtype per WHO 2021 classification and local assessment of tissue from diagnosis or recurrence
- Initial treatment of newly diagnosed glioblastoma by maximal safe resection and postsurgical concurrent conventionally fractionated or abbreviated (minimum 15 fractions) chemoradiotherapy with or without maintenance chemotherapy with temozolomide (patient must have received at least one dose)
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- Stable or decreasing dose of steroids for 7 days prior to enrolment
- Age ≥ 18 years
- WHO Performance status of 0-2
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment.
- Patients of childbearing / reproductive potential must agree to use adequate birth control measures during the study treatment period and for at least 6 months after the last dose of study treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
- Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
- Non-sterile males must use contraception during treatment and for 6 months after the last dose.
- Non-sterile males must avoid sperm donation for the duration of the study and for at least 6 months after the last dose of study treatment.
Who cannot join
- Any prior anticancer treatment for recurrent glioblastoma (except surgery)
- Significant reduction in thrombocyte and/or leukocyte counts as well as severe renal impairment according to investigator's opinion
- History or present acute leukaemia or any myeloid disease
- Known hypersensitivity to the active components or excipients of lomustine
- Known coeliac disease or wheat allergy
- Live attenuated vaccine in the 3 months prior to lomustine initiation
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- Any serious or uncontrolled medical condition (e.g., infections, chronic alcoholism, drug addiction) or abnormality, in the judgment of the investigator that prohibits obtaining informed consent, safe participation and study completion
- Known contraindication to imaging tracer or any product of contrast media and Magnetic Resonance Imaging (MRI) contraindications
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial.
Trial locations and contacts
45 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
45 sites in 11 countries
France10 sites, 10 recruiting
- Recruiting
CHU d'Amiens - CHU Amiens Picardie - Site Sud
Amiens, 80054
- Recruiting
CLCC - Jean Perrin
Clermont-Ferrand, 63000
- Recruiting
CHRU de Lille
Lille, 59037
- Recruiting
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
Lyon
- Recruiting
Institut du Cancer de Montpellier
Montpellier
- Recruiting
CHU de Nice - Hôpital Pasteur
Nice, 06000
- Recruiting
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere (233)
Paris, 75013
- Recruiting
Assistance Publique Hopitaux Paris- APHP - APHP Nord - Univ De Paris Cite - Hop. Saint Louis
Paris
- Recruiting
Institut de Cancerologie de l´Ouest (ICO) - Saint Herblain
Saint-Herblain, 44805
- Recruiting
Institut Public De Cancerologie Strauss Europe-Strauss Institute
Strasbourg, 67200
Roland Schott
Germany9 sites, 6 recruiting
- Recruiting
Univ. Knappschaft Krankenhaus Bochum
Bochum, 44892
- Recruiting
Universitaetsklinikum Koeln
Cologne, 50937
- Terminated
Universitaetsklinikum Erlangen-Schwabachanlage
Erlangen
- Recruiting
Universitaetsklinikum - Essen
Essen, 45147
Sied Kebir
- Recruiting
Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
Heidelberg, 69120
- Terminated
Universitätsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
Leipzig, 04103
- Recruiting
Ludwig-Maximilians-Universitaet Muenchen - Campus Grosshadern
Munich, 81377
- Terminated
Universitaetskliniken Regensburg - Universitaetsklinikum Regensburg
Regensburg, 93053
- Recruiting
Universitaetsklinikum Tuebingen- Crona Kliniken
Tübingen, 72076
Belgium6 sites, 6 recruiting
- Recruiting
AZORG
Aalst, 9300
- Recruiting
Cliniques Universitaires Saint-Luc
Brussels, 1200
- Recruiting
Universitair Ziekenhuis Gent
Ghent, 9000
- Recruiting
Grand Hopital de Charleroi - Site Les Viviers
Gilly, 6060
- Recruiting
U.Z. Leuven - Campus Gasthuisberg
Leuven, 3000
- Recruiting
Ziekenhuis aan de Stroom (ZAS) - ZAS Augustinus (previous GZA)
Wilrijk, 2610
Katrien Erven
Italy5 sites, 5 recruiting
- Recruiting
IRCCS-Ospedale Bellaria-Bologna
Bologna, 40139
- Recruiting
ULSS 9 Scaligera Veneto - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
Legnago, 37045
- Recruiting
Istituto Clinico Humanitas
Milan, 20089
- Recruiting
IRCCS - Istituto Oncologico Veneto
Padova, 35128
- Recruiting
Azienda ospedaliero Univ Policlinico Umberto I
Roma, 00161
Austria3 sites, 3 recruiting
- Recruiting
A.O Landeskrankenhaus - Innsbruck Universitaetsklinik
Innsbruck, 6020
- Recruiting
Kepler University Hospital - Neuromed campus
Linz, 4020
- Recruiting
Universitaetsklinikum Wien - AKH unikliniken
Vienna
Netherlands3 sites, 3 recruiting
- Recruiting
Leiden University Medical Centre
Leiden
- Recruiting
Erasmus MC
Rotterdam
- Recruiting
ETZ Tilburg - ETZ - St. Elisabethziekenhuis
Tilburg, 5022
Spain3 sites, 3 recruiting
- Recruiting
Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia) (381)
Badalona, 08916
- Recruiting
ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
L'Hospitalet de Llobregat, 08908
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Norway2 sites, 2 recruiting
- Recruiting
Oslo University Hospital - Radiumhospitalet
Oslo, NO 0379
- Recruiting
St Olavs University Hospital - St. Olavs Hospital, Trondheim University Hospital
Trondheim, NO 7030
Switzerland2 sites, 2 recruiting
- Recruiting
Oncology Institute of Southern Switzerland (IOSI) - Ospedale San Giovanni
Bellinzona, 6500
- Recruiting
UniversitaetsSpital Zurich - Neurology Clinic
Zurich, 8091
Emilie Le Rhun
Denmark1 site, 1 recruiting
- Recruiting
Aarhus University Hospitals - Region Midtjylland - Aarhus University Hospital-Skejby
Aarhus, 8200
About this study
Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.
- Conditions
- First Progression of Glioblastoma
- Being tested
- Lomustine, Reirradiation
- Keywords
- First progression, Glioblastoma, Phase III, Lomustine, Reirradiation
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LomustineDrug
Oral administration of Lomustine
ReirradiationRadiation
Given at least 6 months after the end of prior radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Lomustine alone Receives: Drug: Lomustine |
| Experimental group | Experimental | Lomustine plus reirradiation Receives: Drug: Lomustine; Radiation: Reirradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Defined as the number of days from date of enrolment to the date of death due to any cause
Measured: From the date of enrolment up to the date of death, assessed up to 40 months after first patient is enrolled
Secondary outcomes (7)
Progression Free Survival (PFS)
Events are progressions based on Response Assessment in Neuro Oncology (RANO) criteria as determined by the local investigator .
Measured: From the date of enrolment up to the date of first objective progression or the date of death whichever occur first, assessed up to 40 months after first patient is enrolled
Health-related Quality of Life (HRQoL)
HRQoL will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3.
Measured: From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
Toxicity profile of lomustine plus reirradiation
Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting.
Measured: From the date of enrolment until end of study treatment 30 (± 7 days) after last dose, assessed up to 40 months after first patient is enrolled
Neurocognitive functioning of lomustine pus reirradiation
Neurocognitive functioning assessed by Mini Mental State Examination (MMSE)
Measured: From the date of enrolment until end of study treatment 30 (± 7 days) after last dose, assessed up to 40 months after first patient is enrolled
To transform self-reported quality of life data from the QLQ-C30 into health utility values, ready to be used in subsequent health economic analyses.
A deterioration event is defined as ≥>10-point worsening from baseline in the GHQ without further improvement (i.e., no subsequent ≥>10 point improvement) or death due to any cause.
Measured: From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
Objective response (ORR)
Measured: From the date of enrolment up to the date of first objective progression or the date of death whichever occur first, assessed up to 40 months after first patient is enrolled
Complete response (CRR)
Measured: From the date of enrolment up to the date of first objective progression or the date of death whichever occur first, assessed up to 40 months after first patient is enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start15 Mar 2024
- Primary completionSep 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for First Progression of GlioblastomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 411 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Swiss Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Matthias Preusser, Prof., Principal investigator, EORTC Study CoordinatorGiuseppe Minniti, Dr., Principal investigator, EORTC Study Coordinator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05904119
- Sponsor's protocol ID
- EORTC-2227-BTG
- Acronym
- LEGATO
- Status last verified
- Jun 2026
- First submitted
- 23 May 2023
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Preusser M, Kazda T, Le Rhun E, Sahm F, Smits M, Gempt J, Koekkoek JA, Monti AF, Csanadi M, Pitter JG, Bulbek H, Fournier B, Quoilin C, Gorlia T, Weller M, Minniti G; European Organisation for Research, Treatment of Cancer (EORTC) Brain Tumor Group. Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study. Trials. 2024 Jun 7;25(1):366. doi: 10.1186/s13063-024-08213-7.
PubMed 38849943