Clinical trial NCT05904119: Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study
Official title: Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: First Progression of Glioblastoma
Keywords: First progression
Glioblastoma
Phase III
Lomustine
Reirradiation
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Swiss Group for Clinical Cancer Research
First posted: 2023-06-15
Enrollment: 411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of enrolment up to the date of death, assessed up to 40 months after first patient is enrolled
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Health-related Quality of Life (HRQoL)
timeFrame: From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
measure: Toxicity profile of lomustine plus reirradiation
timeFrame: 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
measure: Neurocognitive functioning of lomustine pus reirradiation
timeFrame: 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
measure: 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.
timeFrame: From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
measure: Objective response (ORR)
timeFrame: 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
measure: Complete response (CRR)
timeFrame: 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
Other outcomes:
measure: To assess health-related quality of life over time based on the results of 3 different scales (QLQ-C30, QLQ-BN20 and the item list (IL46)).
timeFrame: From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
Locations:
city: Innsbruck
country: Austria
facility: A.O Landeskrankenhaus - Innsbruck Universitaetsklinik
city: Linz
country: Austria
facility: Kepler University Hospital - Neuromed campus
city: Vienna
country: Austria
facility: Universitaetsklinikum Wien - AKH unikliniken
city: Aalst
country: Belgium
facility: AZORG
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gilly
country: Belgium
facility: Grand Hopital de Charleroi - Site Les Viviers
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Brno
country: Czechia
facility: Masaryk Memorial Cancer Institute
city: Aarhus
country: Denmark
facility: Aarhus University Hospitals - Region Midtjylland - Aarhus University Hospital-Skejby
city: Amiens
country: France
facility: CHU d'Amiens - CHU Amiens Picardie - Site Sud
city: Clermont-Ferrand
country: France
facility: CLCC - Jean Perrin
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur
city: Paris
country: France
facility: Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere (233)
city: Paris
country: France
facility: Assistance Publique Hopitaux Paris- APHP - APHP Nord - Univ De Paris Cite - Hop. Saint Louis
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de l´Ouest (ICO) - Saint Herblain
city: Bochum
country: Germany
facility: Univ. Knappschaft Krankenhaus Bochum
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen-Schwabachanlage
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
city: Munich
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen - Campus Grosshadern
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen- Crona Kliniken
city: Bologna
country: Italy
facility: IRCCS-Ospedale Bellaria-Bologna
city: Legnago
country: Italy
facility: ULSS 9 Scaligera Veneto - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Padova
country: Italy
facility: IRCCS - Istituto Oncologico Veneto
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol (Institut Catala D&amp;#39;Oncologia)
state: Barcelona
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia) (381)
city: Hospitalet De Llobregat
country: Spain
facility: ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: EORTC Study Coordinator
name: Matthias Preusser, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: EORTC Study Coordinator
name: Giuseppe Minniti, Dr.
role: PRINCIPAL_INVESTIGATOR
References: