Clinical trial • Phase III • Oncology

Lomustine for Glioblastoma

Phase III trial of Lomustine for Glioblastoma.

Overview

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

Key dates

Initial CTIS Submission Date
12-10-2023
First CTIS Authorization Date
20-02-2024

Trial design

Randomised, lomustine monotherapy versus lomustine plus reirradiation. lomustine is administered orally (dose units mg/m2; product metadata lists max total dose amount 200 mg and dose uom mg/m2). reirradiation is radiotherapy added to lomustine in the combination arm. (no detailed dose-schedule for lomustine or radiotherapy schedule provided in the ctis data.)-controlled Phase III trial in Austria, Czechia, Netherlands and others.

Randomised
Yes
Comparator
Lomustine monotherapy versus lomustine plus reirradiation. Lomustine is administered orally (dose units mg/m2; product metadata lists max total dose amount 200 mg and dose UoM mg/m2). Reirradiation is radiotherapy added to lomustine in the combination arm. (No detailed dose-schedule for lomustine or radiotherapy schedule provided in the CTIS data.)
Target Sample Size
383

Eligibility

Recruits 383 Written informed consent must be given according to ICH/GCP and national/local regulations. Vulnerable population not selected for the study (isVulnerablePopulationSelected: false). Consent materials / ICFs are provided in multiple country languages and, where required, witnesses/interpreters have been used (documented in unexpected events)..

Pregnancy Exclusion
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to enrolment
Vulnerable Population
Written informed consent must be given according to ICH/GCP and national/local regulations. Vulnerable population not selected for the study (isVulnerablePopulationSelected: false). Consent materials / ICFs are provided in multiple country languages and, where required, witnesses/interpreters have been used (documented in unexpected events).

Inclusion criteria

  • {"criterion_text":"- Before patient’s enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.\n- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to enrolment\n- Candidates for treatment with lomustine as per physician’s assessment.\n- 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.\n- Patients with first progression or recurrent glioblastoma after first-line treatment with biopsy or maximal safe resection and standard radiotherapy or chemoradiotherapy with recurrence occuring at least 6 months after the end of Prior radiotherapy Prior first line therapy may include: Any systemic antineoplastic treatment other than nitroureas , Tumour-treating fields, Conventionally fractionated or abbreviated (minimum 15 fractions) radiotherapy\n- Measurable disease according to RANO criteria with a maximum tumour diameter of 5 cm (local investigator assessment) Note 1: in case of multiple lesions, maximum cumulative CTV diameter of 5 cm treatable by 1 isocentre. Note 2: in case of surgery for recurrence, this criterion applies at the time of recurrence.\n- 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. Note: residual and measurable disease after surgery is not required, provided that measurable disease was present before surgery.\n- Histologically proven diagnosis of glioblastoma, IDH wildtype per WHO 2021 classification and local assessment of tissue from diagnosis or recurrence\n- Stable or decreasing dose of steroids for 7 days prior to enrolment\n- Age ≥ 18 years\n- WHO Performance status of 0-2"}

Exclusion criteria

  • {"criterion_text":"- Any prior anticancer treatment for recurrent glioblastoma (except surgery)\n- 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\n- Known contraindication to imaging tracer or any product of contrast media and Magnetic Resonance Imaging (MRI) contraindications\n- 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\n- Concurrent or recent history (30 days prior to lomustine initiation) of varicella (infection or exposure) and herpes zoster\n- Known hereditary galactose intolerance, Lapp-lactase deficiency, or glucose-galactose malabsorption.\n- Patients with known pulmonary infiltration, interstitial pneumonia or pulmonary fibrosis and with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO)\n- Significant reduction in thrombocyte and/or leukocyte counts (leukocytes < 4 x 10^9 /L and the platelets < 100 x 10^9 /L) as well as severe renal impairment according to investigator's opinion\n- History or present acute leukaemia or any myeloid disease\n- Known hypersensitivity to the active components or excipients of lomustine\n- Known coeliac disease or wheat allergy\n- Live attenuated vaccine in the 3 months prior to lomustine initiation"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is OS defined as the number of days from date of enrolment to the date of death due to any cause.","definition_or_measurement_approach":"OS defined as the number of days from date of enrolment to the date of death due to any cause."}

Secondary endpoints

  • {"endpoint_text":"- PFS. Events are progressions based on Response Assessment in Neuro Oncology (RANO) criteria as determined by the local investigator","definition_or_measurement_approach":"Progression-free survival; events = progressions based on RANO criteria as determined by the local investigator."}
  • {"endpoint_text":"- Objective and complete response per RANO criteria as assessed by the local investigator","definition_or_measurement_approach":"Objective and complete tumour response assessed locally per RANO criteria."}
  • {"endpoint_text":"- Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting","definition_or_measurement_approach":"Safety assessed using CTCAE v5.0 for toxicity and SAE reporting."}
  • {"endpoint_text":"- QDFS. 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","definition_or_measurement_approach":"QoL deterioration-free survival (QDFS); deterioration event = ≥10-point worsening from baseline in global health quality (GHQ) without subsequent ≥10-point improvement, or death."}
  • {"endpoint_text":"- Neurocognitive functioning assessed by Mini Mental State Examination (MMSE).","definition_or_measurement_approach":"Neurocognitive function measured by MMSE."}
  • {"endpoint_text":"- Health utility, calculated from the collected patient-reported HRQoL data from the QLQ-C30 and patient demographics","definition_or_measurement_approach":"Health utility values derived from QLQ-C30 patient-reported HRQoL data and patient demographics for health economic analyses."}
  • {"endpoint_text":"- Change scores. Changes in HRQoL from baseline in the GHQ/QoL, fatigue, nausea/vomiting, physical, role and social functioning scale scores assessed over time will be evaluated descriptively. Descriptive summaries such as median, range (minimum, maximum), IQR, mean and standard deviation will be provided for all the other scales from the QLQ-C30, QLQ-BN20 and the item list (IL46).","definition_or_measurement_approach":"Descriptive evaluation of changes from baseline in HRQoL scale scores (GHQ/QoL, fatigue, nausea/vomiting, physical, role, social functioning) with descriptive statistics (median, range, IQR, mean, SD) for QLQ-C30, QLQ-BN20, IL46 scales."}

Recruitment

Planned Sample Size
383
Recruitment Window Months
47
Consent Approach
Written informed consent must be given according to ICH/GCP and national/local regulations. Consent is provided by adult participants (study includes age ≥18). Subject information sheets and ICFs are available in multiple languages (documents in DE, IT, ES, DA, NL, FR, NO, CS, EN and country-specific ICFs are listed). Where needed, witnesses/interpreters have been used (documented unexpected event: enrolment of a non-French-speaking patient with witness/interpreter present).

Geography

Total Number Of Sites
41
Total Number Of Participants
371

Austria

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
26-02-2024
Processing Time Days
28
Number Of Sites
3
Number Of Participants
32

Sites

Site Name
Medizinische Universitaet Innsbruck
Department Name
Neurology
Principal Investigator Name
Meinhard Nevinny-Stickel
Principal Investigator Email
meinhard.nevinny@i-med.ac.at
Contact Person Name
Meinhard Nevinny-Stickel
Contact Person Email
meinhard.nevinny@i-med.ac.at
Site Name
Kepler Universitaetsklinikum GmbH
Department Name
Neurology
Principal Investigator Name
Josef Pichler
Principal Investigator Email
josef.pichler@kepleruniklinikum.at
Contact Person Name
Josef Pichler
Site Name
Medical University of Vienna
Department Name
Oncology
Principal Investigator Name
Anna Berghoff
Principal Investigator Email
anna.berghoff@meduniwien.ac.at
Contact Person Name
Anna Berghoff
Contact Person Email
anna.berghoff@meduniwien.ac.at

Czechia

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
20-02-2024
Processing Time Days
22
Number Of Sites
1
Number Of Participants
7

Sites

Site Name
Masarykuv Onkologicky Ustav
Department Name
Oncology
Principal Investigator Name
Tomas Kazda
Principal Investigator Email
tomas.kazda@mou.cz
Contact Person Name
Tomas Kazda
Contact Person Email
tomas.kazda@mou.cz

Netherlands

Earliest CTIS Part Ii Submission Date
15-02-2024
Latest Decision Or Authorization Date
21-02-2024
Processing Time Days
6
Number Of Sites
3
Number Of Participants
37

Sites

Site Name
St. Elisabeth Hospital Tilburg
Department Name
Oncology
Principal Investigator Name
Laurens Beerepoot
Principal Investigator Email
L.Beerepoot@etz.nl
Contact Person Name
Laurens Beerepoot
Contact Person Email
L.Beerepoot@etz.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Oncology
Principal Investigator Name
Marjolein Geurts
Principal Investigator Email
m.geurts@erasmusmc.nl
Contact Person Name
Marjolein Geurts
Contact Person Email
m.geurts@erasmusmc.nl
Site Name
Leiden University Medical Center
Department Name
Oncology
Principal Investigator Name
Josefine Schopman
Principal Investigator Email
j.e.schopman@lumc.nl
Contact Person Name
Josefine Schopman
Contact Person Email
j.e.schopman@lumc.nl

Italy

Earliest CTIS Part Ii Submission Date
26-01-2024
Latest Decision Or Authorization Date
20-02-2024
Processing Time Days
25
Number Of Sites
6
Number Of Participants
62

Sites

Site Name
Istituto Oncologico Veneto
Department Name
Oncology
Principal Investigator Name
Giuseppe Lombardi
Principal Investigator Email
giuseppe.lombardi@iov.veneto.it
Contact Person Name
Giuseppe Lombardi
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
Radiation-Oncology Unit
Principal Investigator Name
Lorenzo Livi
Principal Investigator Email
lorenzo.livi@unifi.it
Contact Person Name
Lorenzo Livi
Contact Person Email
lorenzo.livi@unifi.it
Site Name
Universita' Degli Studi Di Roma La Sapienza
Department Name
Oncology
Principal Investigator Name
Giuseppe Minniti
Principal Investigator Email
giuseppe.minniti@uniroma.it
Contact Person Name
Giuseppe Minniti
Contact Person Email
giuseppe.minniti@uniroma.it
Site Name
Instituto Di Ricovero E Cura A Carattere Scientifico
Department Name
Oncology
Principal Investigator Name
Enrico Franceschi
Principal Investigator Email
e.franceschi@ausl.bo.it
Contact Person Name
Enrico Franceschi
Contact Person Email
e.franceschi@ausl.bo.it
Site Name
Ospedale Mater Salutis Di Legnago
Department Name
Radiation oncology
Principal Investigator Name
Francesco Fiorica
Principal Investigator Email
francesco.fiorica@aulss9.veneto.it
Contact Person Name
Francesco Fiorica
Site Name
Humanitas Research Hospital
Department Name
Radiation oncology
Principal Investigator Name
Pierina Navarria
Principal Investigator Email
piera.navarria@cancercenter.humanitas.it
Contact Person Name
Pierina Navarria

Spain

Earliest CTIS Part Ii Submission Date
15-01-2024
Latest Decision Or Authorization Date
21-02-2024
Processing Time Days
37
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Principal Investigator Name
Virginia Rodriguez
Principal Investigator Email
virginia.rod.gon@gmail.com
Contact Person Name
Virginia Rodriguez
Contact Person Email
virginia.rod.gon@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncology
Principal Investigator Name
Anna Lucas Calduch
Principal Investigator Email
alucas@iconcologia.net
Contact Person Name
Anna Lucas Calduch
Contact Person Email
alucas@iconcologia.net
Site Name
Hospital Germans Trias I Pujol
Department Name
Oncology
Principal Investigator Name
Silvia Comas Anton
Principal Investigator Email
scomas@iconcologia.net
Contact Person Name
Silvia Comas Anton
Contact Person Email
scomas@iconcologia.net

Belgium

Earliest CTIS Part Ii Submission Date
24-01-2024
Latest Decision Or Authorization Date
22-02-2024
Processing Time Days
29
Number Of Sites
6
Number Of Participants
33

Sites

Site Name
Azorg
Department Name
Oncology
Principal Investigator Name
Samuel Bral
Principal Investigator Email
Samuel.Bral@azorg.be
Contact Person Name
Samuel Bral
Contact Person Email
Samuel.Bral@azorg.be
Site Name
UZ Leuven
Department Name
Oncology
Principal Investigator Name
Maarten Lambrecht
Principal Investigator Email
maarten.lambrecht@uzleuven.be
Contact Person Name
Maarten Lambrecht
Contact Person Email
maarten.lambrecht@uzleuven.be
Site Name
Ziekenhuis Aan De Stroom
Department Name
Oncology Centre
Principal Investigator Name
Katrien Erven
Principal Investigator Email
katrien.erven@zas.be
Contact Person Name
Katrien Erven
Contact Person Email
katrien.erven@zas.be
Site Name
Grand Hopital De Charleroi
Department Name
Oncology
Principal Investigator Name
Vincent Verschaeve
Principal Investigator Email
vincent.verschaeve@ghdc.be
Contact Person Name
Vincent Verschaeve
Contact Person Email
vincent.verschaeve@ghdc.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Oncology
Principal Investigator Name
Dario Di Perri
Principal Investigator Email
dario.diperri@saintluc.uclouvain.be
Contact Person Name
Dario Di Perri
Site Name
Universitair Ziekenhuis Gent
Department Name
Radiotherapy
Principal Investigator Name
Tom Boterberg
Principal Investigator Email
tom.boterberg@ugent.be
Contact Person Name
Tom Boterberg
Contact Person Email
tom.boterberg@ugent.be

France

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
26-02-2024
Processing Time Days
75
Number Of Sites
9
Number Of Participants
97

Sites

Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Medical Oncology
Principal Investigator Name
Mathieu Boone
Principal Investigator Email
boone.mathieu@chu-amiens.fr
Contact Person Name
Mathieu Boone
Contact Person Email
boone.mathieu@chu-amiens.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Radiotherapy
Principal Investigator Name
Florine Tomaszewski
Principal Investigator Email
Florine.tomaszewski@ico.unicancer.fr
Contact Person Name
Florine Tomaszewski
Site Name
Institut De Cancerologie Strasbourg Europe
Department Name
Medical Oncology
Principal Investigator Name
Roland Schott
Principal Investigator Email
r.schott@icans.eu
Contact Person Name
Roland Schott
Contact Person Email
r.schott@icans.eu
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Neurology
Principal Investigator Name
Véronique Bourg
Principal Investigator Email
bourg.v@chu-nice.fr
Contact Person Name
Véronique Bourg
Contact Person Email
bourg.v@chu-nice.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Neurology
Principal Investigator Name
Apolline Monfilliette-Djelad
Principal Investigator Email
apolline.djelad@chru-lille.fr
Contact Person Name
Apolline Monfilliette-Djelad
Contact Person Email
apolline.djelad@chru-lille.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Radiation oncology
Principal Investigator Name
Julian Jacob
Principal Investigator Email
Julian.jacob@aphp.fr
Contact Person Name
Julian Jacob
Contact Person Email
Julian.jacob@aphp.fr
Site Name
Hospices Civils De Lyon
Department Name
Neuro-Oncology
Principal Investigator Name
François Ducray
Principal Investigator Email
francois.ducray@chu-lyon.fr
Contact Person Name
François Ducray
Contact Person Email
francois.ducray@chu-lyon.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neurology
Principal Investigator Name
Stefania Cuzzubbo
Principal Investigator Email
stefania.cuzzubbo@aphp.fr
Contact Person Name
Stefania Cuzzubbo
Contact Person Email
stefania.cuzzubbo@aphp.fr
Site Name
Centre Jean Perrin
Department Name
Oncology & Clinical Research
Principal Investigator Name
Xavier Durando
Principal Investigator Email
xavier.durando@clermont.unicancer.fr
Contact Person Name
Xavier Durando

Denmark

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
20-02-2024
Processing Time Days
7
Number Of Sites
1
Number Of Participants
7

Sites

Site Name
Region Midtjylland
Department Name
clinical oncology
Principal Investigator Name
Slavka Lucacova
Principal Investigator Email
slvkluka@rm.dk
Contact Person Name
Slavka Lucacova
Contact Person Email
slvkluka@rm.dk

Germany

Earliest CTIS Part Ii Submission Date
14-02-2024
Latest Decision Or Authorization Date
21-02-2024
Processing Time Days
7
Number Of Sites
7
Number Of Participants
56

Sites

Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Neurology
Principal Investigator Name
Ghazaleh Tabatabai
Principal Investigator Email
ghazaleh.tabatabai@uni-tuebingen.de
Contact Person Name
Ghazaleh Tabatabai
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Neurology
Principal Investigator Name
Louisa Von Baumgarten
Principal Investigator Email
Louisa.vonBaumgarten@med.uni-muenchen.de
Contact Person Name
Louisa Von Baumgarten
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Neurology
Principal Investigator Name
Antje Wick
Principal Investigator Email
antje.wick@med.uni-heidelberg.de
Contact Person Name
Antje Wick
Site Name
Universitaetsklinikum Essen AöR
Department Name
Neurology
Principal Investigator Name
Sied Kebir
Principal Investigator Email
sied.kebir@uk-essen.de
Contact Person Name
Sied Kebir
Contact Person Email
sied.kebir@uk-essen.de
Site Name
Universitaetsklinikum Knappschaftskrankenhaus Bochum GmbH
Department Name
Neurology
Principal Investigator Name
Corinna Seliger-Behme
Principal Investigator Email
corinna.seliger-Behme@kk-bochum.de
Contact Person Name
Corinna Seliger-Behme
Site Name
University Hospital Cologne AöR
Department Name
Neurology
Principal Investigator Name
norbert galldiks
Principal Investigator Email
norbert.galldiks@uk-koeln.de
Contact Person Name
norbert galldiks
Contact Person Email
norbert.galldiks@uk-koeln.de
Site Name
Universitaetsklinikum Jena KöR
Department Name
Neurosurgery
Principal Investigator Name
Christian Senft
Principal Investigator Email
christian.senft@med.uni-jena.de
Contact Person Name
Christian Senft

Norway

Earliest CTIS Part Ii Submission Date
24-01-2024
Latest Decision Or Authorization Date
20-02-2024
Processing Time Days
27
Number Of Sites
2
Number Of Participants
20

Sites

Site Name
Oslo University Hospital HF
Department Name
Oncology
Principal Investigator Name
Petter Brandal
Principal Investigator Email
petter.brandal@ous-hf.no
Contact Person Name
Petter Brandal
Contact Person Email
petter.brandal@ous-hf.no
Site Name
St. Olavs Hospital HF
Department Name
Oncology
Principal Investigator Name
Tora S. Solheim
Principal Investigator Email
tora.s.solheim@ntnu.no
Contact Person Name
Tora S. Solheim
Contact Person Email
tora.s.solheim@ntnu.no

Sponsor

Primary sponsor

Full Name
European Organisation For Research And Treatment Of Cancer
Organisation Type
Patient organisation/association
Country Of Registered Address
Belgium

Third parties

  • {"country":"United Kingdom","full_name":"Klinikos Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
LOMUSTINE
Active Substance
Lomustine
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
200 mg
Combination Treatment
Yes

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