NCT05904119Recruiting

Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study

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. 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.

Inclusion criteria

• 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) • 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.

Exclusion criteria

• 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 • 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.

Contacts

The trial team's contact details are shown on request.

See the official trial record

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Countries: Switzerland, France, Germany, Italy, Austria, Belgium, Czechia, Denmark, Netherlands, Norway, Spain
Sponsor: European Organisation for Research and Treatment of Cancer - EORTC(Network / cooperative)
Protocol no.: EORTC-2227-BTG
Conditions: First Progression of Glioblastoma
Interventions: Drug, Radiation

Treatments studied

Lomustine
Reirradiation

Collaborators

Swiss Cancer Institute

Locations · 42

Bellinzona, SwitzerlandOncology Institute of Southern Switzerland (IOSI) - Ospedale San GiovanniRecruiting at this site
Zurich, SwitzerlandUniversitaetsSpital Zurich - Neurology ClinicRecruiting at this site
Amiens, FranceCHU d'Amiens - CHU Amiens Picardie - Site SudRecruiting at this site
Clermont-Ferrand, FranceCLCC - Jean PerrinRecruiting at this site
Lille, FranceCHRU de LilleRecruiting at this site
Lyon, FranceCHU de Lyon - CHU Lyon - Hopital neurologique Pierre WertheimerRecruiting at this site
Montpellier, FranceInstitut du Cancer de MontpellierRecruiting at this site
Nice, FranceCHU de Nice - Hôpital PasteurRecruiting at this site
Paris, FranceAssistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere (233)Recruiting at this site
Paris, FranceAssistance Publique Hopitaux Paris- APHP - APHP Nord - Univ De Paris Cite - Hop. Saint LouisRecruiting at this site
Saint-Herblain, FranceInstitut de Cancerologie de l´Ouest (ICO) - Saint HerblainRecruiting at this site
Strasbourg, FranceInstitut Public De Cancerologie Strauss Europe-Strauss InstituteRecruiting at this site
Bochum, GermanyUniv. Knappschaft Krankenhaus BochumRecruiting at this site
Cologne, GermanyUniversitaetsklinikum KoelnRecruiting at this site
Essen, GermanyUniversitaetsklinikum - EssenRecruiting at this site
Heidelberg, GermanyUniversitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head HospitalRecruiting at this site
Munich, GermanyLudwig-Maximilians-Universitaet Muenchen - Campus GrosshadernRecruiting at this site
Tübingen, GermanyUniversitaetsklinikum Tuebingen- Crona KlinikenRecruiting at this site
Bologna, ItalyIRCCS-Ospedale Bellaria-BolognaRecruiting at this site
Legnago, ItalyULSS 9 Scaligera Veneto - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis HospitalRecruiting at this site
Milan, ItalyIstituto Clinico HumanitasRecruiting at this site
Padova, ItalyIRCCS - Istituto Oncologico VenetoRecruiting at this site
Roma, ItalyAzienda ospedaliero Univ Policlinico Umberto IRecruiting at this site
Innsbruck, AustriaA.O Landeskrankenhaus - Innsbruck UniversitaetsklinikRecruiting at this site
Linz, AustriaKepler University Hospital - Neuromed campusRecruiting at this site
Vienna, AustriaUniversitaetsklinikum Wien - AKH uniklinikenRecruiting at this site
Aalst, BelgiumAZORGRecruiting at this site
Brussels, BelgiumCliniques Universitaires Saint-LucRecruiting at this site
Ghent, BelgiumUniversitair Ziekenhuis GentRecruiting at this site
Gilly, BelgiumGrand Hopital de Charleroi - Site Les ViviersRecruiting at this site

In total, worldwide, 42 of the 45 sites listed in the registry are recruiting; the other 3 are not currently recruiting.

Site status per the ClinicalTrials.gov registry (last update posted: June 8, 2026).

This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.

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These results are indicative and do not replace medical advice — discuss them with your doctor.