Clinical trial • Phase III • Oncology|Neurology

lomustine for Glioblastoma

Phase III trial of lomustine for Glioblastoma.

Overview

Trial Therapeutic Area
Oncology|Neurology
Trial Disease
Glioblastoma
Trial Stage
Phase III
Drug Modality
Small molecule|Small molecule

Key dates

Initial CTIS Submission Date
12-12-2023
First CTIS Authorization Date
04-04-2024

Trial design

Randomised, tmz monochemotherapy plus standard radiotherapy +/- concomitant ttfields (optune) (comparator arm as described in title; dosing/schedule not specified in provided data)-controlled Phase III trial in Austria, Denmark, Sweden and others.

Randomised
Yes
Comparator
TMZ monochemotherapy plus standard radiotherapy +/- concomitant TTFields (Optune) (comparator arm as described in title; dosing/schedule not specified in provided data)
Biomarker Stratified
True, MGMT promoter methylation
Target Sample Size
200
Trial Duration For Participant
1095

Eligibility

Recruits 200 Written informed consent is required; participants must be capable of understanding the rationale and necessity of study therapy and procedures. The trial does not select vulnerable populations (isVulnerablePopulationSelected: false) and no assent procedures for minors are described (age inclusion is 18-75)..

Pregnancy Exclusion
Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test must be obtained within 14 days prior to treatment start
Vulnerable Population
Written informed consent is required; participants must be capable of understanding the rationale and necessity of study therapy and procedures. The trial does not select vulnerable populations (isVulnerablePopulationSelected: false) and no assent procedures for minors are described (age inclusion is 18-75).

Inclusion criteria

  • {"criterion_text":"- Written informed consent"}
  • {"criterion_text":"- Adequate organ function as described in the protocol"}
  • {"criterion_text":"- Patients on anticoagulation can be included at the discretion of the investigator, but oral anticoagulants, including NOAC/DOAC are recommended to be switched to Low-molecular-weight heparin (LMWH) during the treatment phase and until platelets are >50 or according to local guidelines."}
  • {"criterion_text":"- Patient capable of understanding the rationale and necessity of study therapy and procedures."}
  • {"criterion_text":"- Newly diagnosed histologically proven GBM, giant-cell GBM or gliosarcoma WHO Grad 4, histology confirmed by the local neuropathologist as IDHwt. Histology obtained by complete resection, partial resection, open biopsy or stereotactic biopsy."}
  • {"criterion_text":"- Methylated MGMT promoter in the tumor as determined according to local routine. For centers using the same method/kit the same cut-off for mMGMT will be used."}
  • {"criterion_text":"- Males or females 18-75 years of age, estimated life expectancy of at least 12 weeks"}
  • {"criterion_text":"- WHO Performance Score 0-2"}
  • {"criterion_text":"- Patient compliance and geographic proximity that allow adequate follow up"}
  • {"criterion_text":"- Male and female patients with reproductive potential must use an approved contraceptive method (intrauterine device, birth control pills, or barrier device) during and for 6 months after end of chemotherapy (Pearl index <1%)"}
  • {"criterion_text":"- Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test must be obtained within 14 days prior to treatment start"}

Exclusion criteria

  • {"criterion_text":"- Prior malignancy (except adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer), unless the prior malignancy was diagnosed and curatively treated ≥3 years previously with no subsquent evidence of recurrence"}
  • {"criterion_text":"- Any active infection (at the discretion of the investigator)"}
  • {"criterion_text":"- Female patients that are breastfeeding and not willing to refrain"}
  • {"criterion_text":"- Patients with reproductive potential who do not accept to use contraception during chemotherapy and 6 months thereafter"}
  • {"criterion_text":"- Treatment in another clinical trial with oncological therapeutic intervention or use of any other investigational agent within 30 days before enrolment"}
  • {"criterion_text":"- Any psychological, cognitive, familial, social or geographical condition potentially hampering compliance with the study protocol and follow-up scheduled visits (at the discretion of investigator)"}
  • {"criterion_text":"- Prior systemic chemotherapy with DNA-damaging agents for any cancer"}
  • {"criterion_text":"- Prior RT to the brain"}
  • {"criterion_text":"- Concurrent administration of any other antitumor therapy not described in the protocol"}
  • {"criterion_text":"- Concurrent administration of complementary or alternative drugs"}
  • {"criterion_text":"- Allergy or intolerability of temozolomide, dacarbazine, lomustine or other nitrosourea derivatives including celiac disease and wheat allergy"}
  • {"criterion_text":"- Unable to perform MRI"}
  • {"criterion_text":"- Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)"}
  • {"criterion_text":"- Severly reduced lung function (at the discretion of the investigator)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall survival (OS) as measured from the day of randomisation until death or follow-up of at least 36 months.","definition_or_measurement_approach":"Measured from the day of randomisation until death or follow-up of at least 36 months (OS)."}

Secondary endpoints

  • {"endpoint_text":"- Progression-free survival (PFS) as measured from the day of randomisation until diagnosis of progressive disease determined by MRI (RANO 2.0 criteria)","definition_or_measurement_approach":"Measured from randomisation until diagnosis of progressive disease determined by MRI using RANO 2.0 criteria."}
  • {"endpoint_text":"- Best response rate determined by MRI (RANO 2.0 criteria)","definition_or_measurement_approach":"Best response rate assessed by MRI using RANO 2.0 criteria."}
  • {"endpoint_text":"- Frequency of delay of the next TMZ/LOM or TMZ cycle by more than 2 weeks","definition_or_measurement_approach":"Count/frequency of cycles delayed >2 weeks."}
  • {"endpoint_text":"- Acute toxicity during radiotherapy and chemotherapy +/- TTFields according to CTCAE latest available version at study start","definition_or_measurement_approach":"Toxicity graded according to CTCAE (latest version at study start)."}
  • {"endpoint_text":"- Quality of life, determined by EORTC questionnaires QLQ-30 and BN-20","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 and BN-20 questionnaires."}
  • {"endpoint_text":"- Evaluation of neurocognition determined by CNS Vital Signs","definition_or_measurement_approach":"Neurocognitive function assessed using CNS Vital Signs."}
  • {"endpoint_text":"- Frequency of pseudoprogression","definition_or_measurement_approach":"Frequency/count of pseudoprogression events as determined by imaging/clinical criteria."}
  • {"endpoint_text":"- Location of tumor recurrence in relation to radiotherapy isodose curves","definition_or_measurement_approach":"Mapping tumor recurrence location relative to radiotherapy isodose curves."}
  • {"endpoint_text":"- Dose to hippocampus and healthy brain in relation to QoL and neurocognitive testing","definition_or_measurement_approach":"Dosimetric analysis of hippocampus/healthy brain correlated with QoL and neurocognitive results."}
  • {"endpoint_text":"- Analysis of OS and PFS for the subgroup of patients receiving TTFields in relation to those not receiving TTFields per treatment arm and combined for both treatment arms (all TTFields patients versus all non-TTFields patients)","definition_or_measurement_approach":"Subgroup analysis comparing OS and PFS between patients receiving TTFields versus not, per arm and combined."}
  • {"endpoint_text":"- Evaluation of neurocognition for the subgroup of patients receiving TTFields in relation to those not receiving TTFields per treatment arm and combined for both treatment arms (all TTFields patients versus all non-TTFields patients)","definition_or_measurement_approach":"Subgroup neurocognitive comparison TTFields vs no TTFields per arm and combined."}
  • {"endpoint_text":"- Time to treatment failure, defined as premature stop of study treatment regardless of reason (progressive disease or toxicity)","definition_or_measurement_approach":"Time from randomisation to premature stop of study treatment for any reason (progression or toxicity)."}
  • {"endpoint_text":"- OS in relation to baseline comorbidities","definition_or_measurement_approach":"Analysis of overall survival stratified by baseline comorbidities."}
  • {"endpoint_text":"- Treatment related neurotoxicity evaluated on MRI","definition_or_measurement_approach":"Assessment of neurotoxicity on MRI imaging attributed to treatment."}

Recruitment

Planned Sample Size
200
Recruitment Window Months
84
Consent Approach
Written informed consent from each participant is required; participants must be capable of understanding the rationale and necessity of study therapy and procedures. No assent processes described (trial restricted to adults 18-75). Subject information and consent forms are available in national languages (documents listed include Swedish and Norwegian subject information/consent forms).

Geography

Total Number Of Sites
25
Total Number Of Participants
200

Austria

Earliest CTIS Part Ii Submission Date
22-05-2025
Latest Decision Or Authorization Date
15-09-2025
Processing Time Days
116
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Medical University Of Graz
Department Name
Department of Neurology and Division of Neuroradiology, Vascular and Interventional Radiology
Contact Person Name
Tadeja Urbanic Purkart
Site Name
Johannes Kepler University Linz
Department Name
Kepleruniversitätsklinikum, Neuromed Campus, Konsiliardienst Innere Medizin und Neuroonkologi
Contact Person Name
Isolde Höllmüller
Site Name
Medizinische Universitaet Innsbruck
Department Name
Department of Neurology, Medical University Innsbruck,
Contact Person Name
Martha Nowosielski-Krappinger
Contact Person Email
Martha.nowosielski@i-med.ac.at
Site Name
Noe LGA Gesundheit Region Mitte GmbH
Department Name
Klinische Abteilung für Neurologie Universitätsklinikum St. Pölten - Lilienfeld
Contact Person Name
Stefan Oberndorfer

Denmark

Earliest CTIS Part Ii Submission Date
14-03-2024
Latest Decision Or Authorization Date
08-09-2025
Processing Time Days
543
Number Of Sites
1
Number Of Participants
30

Sites

Site Name
Region Midtjylland
Department Name
Aarhus University Hospital/Dept. of Oncology
Contact Person Name
Slávka Lukacova
Contact Person Email
Slavka.lukacova@auh.rm.dk

Sweden

Earliest CTIS Part Ii Submission Date
14-03-2024
Latest Decision Or Authorization Date
08-09-2025
Processing Time Days
543
Number Of Sites
14
Number Of Participants
120

Sites

Site Name
Region Vaesterbotten
Department Name
Onkologi, Norrlands universitetsjukhus, Umeå
Contact Person Name
Maria Sandström
Contact Person Email
Maria.sandstrom@umu.se
Site Name
Region Vaermland
Department Name
Onkologikliniken, Centralsjukhuset, Karlstad
Contact Person Name
Martin Rydin
Contact Person Email
martin.rydin@regionvarmland.se
Site Name
Karolinska University Hospital
Department Name
Tema Neuro, ME Neurologi, Karolinska universitetssjukhuset, Solna
Contact Person Name
Giuseppe Stragliotto
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
VE Onkologi Skånes universitetssjukhus, Lund
Contact Person Name
Sara Kinhult
Contact Person Email
sara.kinhult@skane.se
Site Name
Malarsjukhuset Eskilstuna
Department Name
Kliniska forskningsenheten (KFE), Onkologkliniken Sörmland
Contact Person Name
Helene Hörberg
Site Name
Region Gaevleborg
Department Name
Onkologkliniken, Gävle sjukhus
Contact Person Name
Kyriaki Christodoulo
Site Name
Laenssjukhuset I Kalmar Region Kalmar Laen
Department Name
Onkologiska kliniken, Länssjukhuset Kalmar
Contact Person Name
Nathalie Skarin
Site Name
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Department Name
Verksamhetsområde Onkologi, Sahlgrenska Universitetssjukhuset
Contact Person Name
Erik Fernström
Contact Person Email
erik.fernstrom@vgregion.se
Site Name
Region Oerebro Laen
Department Name
Onkologiska kliniken, Onkologmottagningen USÖ Universitetssjukhuset
Contact Person Name
David Löfgren
Site Name
Region Joenkoepings Laen
Department Name
Onkologkliniken Länssjukhuset Ryhov
Contact Person Name
Michael Strandeus
Contact Person Email
michael.strandeus@rjl.se
Site Name
Region Dalarna
Department Name
Neurologmottagningen, Medicinkliniken, Falu lasarett, Falun
Contact Person Name
Pernilla Roswall
Site Name
Region Vaesternorrland
Department Name
Sundsvalls sjukhus, Lasarettsvägen 21, 856 43 Sundsvall, Onkologmottagningen
Contact Person Name
Anna Birgersson
Contact Person Email
anna.birgersson@rvn.se
Site Name
Region Oestergoetland
Department Name
Onkologiska kliniken, Universitetssjukhuset i Linköping
Contact Person Name
Florida Parcaoglu
Site Name
Uppsala University Hospital
Department Name
Blod- och tumörsjukdomar, Onkologen, Akademiska Sjukhuset, Uppsala
Contact Person Name
Pernilla Roswall

Norway

Earliest CTIS Part Ii Submission Date
14-03-2024
Latest Decision Or Authorization Date
03-02-2026
Processing Time Days
691
Number Of Sites
6
Number Of Participants
40

Sites

Site Name
Oslo University Hospital HF
Department Name
Dpt. Of Oncology, Oslo University Hospital,
Contact Person Name
Petter Brandal
Contact Person Email
pebra@ous-hf.no
Site Name
Sorlandet Sykehus HF
Department Name
Center for cancer treatment SSHF, Egsveien 100, Kristiansand
Contact Person Name
René van Helvoirt
Contact Person Email
Rene.helvoirt@sshf.no
Site Name
Helse Bergen HF
Department Name
Haukeland universitets hospital oncology department, Bergen
Contact Person Name
Jorunn Brekke
Contact Person Email
jorunn.brekke@helse-bergen.no
Site Name
Helse Stavanger HF
Department Name
Stavanger University hospital, Dept. of Haematology and oncology, Stavanger
Contact Person Name
Line Sagerup Bjorland
Contact Person Email
line.bjorland@sus.no
Site Name
St. Olavs Hospital HF
Department Name
Cancer Clinic, St.Olavs hospital, Prinsesse kristinasgate 13, Trondheim
Contact Person Name
Tora Skeidsvoll Solheim
Contact Person Email
tora.s.solheim@ntnu.no
Site Name
Universitetssykehuset Nord-Norge HF
Department Name
Kreftavdelingen UNN
Contact Person Name
Øyvind Hald
Contact Person Email
Oyvind.Holsbo.Hald@unn.no

Sponsor

Primary sponsor

Full Name
Vaestra Goetalandsregionen
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Sweden

Third parties

  • {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"1","organisation_type":"Educational Institution"}

Co-sponsors

  • Region Oestergoetland

Investigational products

Investigational Product Name
LOMUSTINE
Active Substance
lomustine
Modality
Small molecule
Routes Of Administration
ORAL
Route
oral
Maximum Dose
maxDailyDoseAmount: 100 mg/m2; maxTotalDoseAmount: 600 mg/m2
Investigational Product Name
TEMOZOLOMIDE
Active Substance
temozolomide
Modality
Small molecule
Routes Of Administration
ORAL
Route
oral
Maximum Dose
maxDailyDoseAmount: 200 mg/m2; maxTotalDoseAmount: 9425 mg/m2
Combination Treatment
Yes

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