Newly Diagnosed GlioblastomaPhase 3MIRAGENCT03345095
A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma
A Phase 3 study testing Marizomib, Temozolomide and radiotherapy in people with Newly Diagnosed Glioblastoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 82 sites in 12 countries.
Trial summary
The standard of care for newly diagnosed glioblastoma includes surgery, involved-field radiotherapy, and concomitant and six cycles of maintenance temozolomide chemotherapy, however the prognosis remains dismal. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed Glioblastoma
- What is being tested?
- Marizomib, Temozolomide and radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 749 participants
- Where
- 82 sitesin 12 countries
- Study dates
- 26 Jul 2018to 30 Jun 2023
- 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
- Histologically confirmed newly diagnosed glioblastoma (WHO grade IV)
- Tumor resection (gross total or partial), or biopsy only
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor block or 24 unstained slides for o6-methylguanine-DNA-methyltransferase (MGMT) analysis
- Patient must be eligible for standard TMZ/RT + TMZ
- Karnofsky performance score (KPS) ≥ 70
- Recovered from effects of surgery, postoperative infection and other complications of surgery (if any)
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- The patient is at least 18 years of age on day of signing informed consent
- Stable or decreasing dose of steroids for at least 1 week prior to inclusion
- The patient has a life expectancy of at least 3 months
- Patient has undergone a brain MRI within 14 days of randomization but after intervention (resection or biopsy)
- The patient shows adequate organ functions as assessed by the specified laboratory values within 2 weeks prior to randomization defined as adequate bone marrow, renal and hepatic function within the following ranges:
- white blood cell count (WBC) ≥ 3×10*9/L
- absolute neutrophil count (ANC) ≥ 1.5×10*9/L
- Platelet count of ≥ 100×10*9/L independent of transfusion
- Hemoglobin ≥ 10 g/dl
- Total Bilirubin ≤ 1.5 upper limit of normal (ULN)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤ 2.5 × ULN
- Serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 30 mL/min(using the Cockcroft-Gault formula)
- Women of child bearing potential (WOCBP) must have a negative urine or 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, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1 percent per year) when used consistently and correctly. Patients must also agree not to donate sperm during the study and for 6 months after receiving the last dose of study treatment.
- Women who are breast feeding must agree to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
- Ability to take oral medication
- Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
- Before patient registration/randomization, written informed consent must be given according to International Council for Harmonisation (ICH) / Good clinical practice (GCP), and national/local regulations.
Who cannot join
None listed.
Trial locations and contacts
82 sites in 12 countries.
82 sites in 12 countries
Canada23 sites
BCCA - Abbotsford Centre
Abbotsford British Columbia
Tom Baker Cancer Centre
Calgary, AB T2N 4N2
Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital
Greater Sudbury
QEII Health Sciences Centre-Capital District Health Authority
Halifax, CA B3H 1V7
Hamilton Health Sciences, Juravinski Cancer Centre
Hamilton
Kingston Health Sciences Centre
Kingston, CA K7L 2V7
London Regional Cancer Center
London, Ontario, N6A 4L6
Montreal Neurological Institute and Hospital McGill University
Montreal, H3A 2B4
CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
Montreal
Hopital Du Sacre-Coeur De Montreal
Montreal
Ottawa Health Research Institute
Ottawa, Ontario, K1Y 4K7
CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
Québec
Allan Blair Cancer Centre
Regina
Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2
Sault Area Hospital
Sault Ste. Marie
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
Odette Cancer Centre - Sunnybrook Health Sciences Centre
Toronto
University Health Network - Oci / Princess Margaret Hospital
Toronto
Centre hospitalier regional de Trois-Rivieres
Trois-Rivières
BC Cancer Agency
Vancouver, V5Z4E9
Bcca - Vancouver Island Cancer Centre
Victoria, BC V8R 6V5
Windsor Regional Cancer Centre
Windsor, Ontario
Cancercare Manitoba
Winnipeg
Germany10 sites
Universitaetsklinikum Bonn
Bonn, 53105
Universitaetsklinik Erlangen-Neurologische Klinik
Erlangen, 91054
Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie
Frankfurt, 60528
UniversitaetsKlinikum Heidelberg - Head Hospital
Heidelberg, 69120
Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
Leipzig, 04103
Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
Mainz, 55131
UniversitaetsMedizin Mannheim
Mannheim, 68167
Technische Universitaet Muenchen - Klinikum Rechts Der Isar
München, 81675
Universitaetskliniken Regensburg
Regensburg, 93053
Universitaetsklinikum Tuebingen- Crona Kliniken
Tübingen, 72076
United States9 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
University of Florida
Gainesville, Florida, 32610
Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute
Hershey, Pennsylvania, 17033
Mayo Clinic
Jacksonville, Florida, 32224-9980
University of California at Irvine
Orange, California, 92868
Mayo Clinic
Rochester, Minnesota, 55905
University of California
San Francisco, California, 94143-0372
John Wayne Cancer Institute
Santa Monica, California, 90404
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
Netherlands9 sites
Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
Amsterdam
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
Amsterdam
Catharina Ziekenhuis
Eindhoven, North Brabant, 5602
University Medical Center Groningen
Groningen
Academisch Ziekenhuis Maastricht
Maastricht, 6202
Radboud University Medical Center Nijmegen
Nijmegen, 6525
Erasmus MC
Rotterdam
Medisch Centrum Haaglanden - Westeinde
The Hague, 2501
Universitair Medisch Centrum - Academisch Ziekenhuis
Utrecht, 3584
Belgium7 sites
Onze Lieve Vrouw Ziekenhuis
Aalst, 9300
GasthuisZusters Antwerpen - Sint-Augustinus
Antwerp
Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
Brussels, 1070
Cliniques Universitaires Saint-Luc
Brussels
Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame
Charleroi
Universitair Ziekenhuis Gent
Ghent, 9000
C.H.U. Sart-Tilman
Liège
France6 sites
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
Bron, 69677
Centre Hospitalier Departemental Vendée
La Roche-sur-Yon, Vendee, 85925
CHRU de Lille
Lille
Institut de Cancerologie de l'Ouest
Nantes
Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
Paris
Gustave Roussy
Villejuif
Spain5 sites
Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
Badalona
Hospital Clinic Universitari de Barcelona
Barcelona, 08036
Institut Catala D'Oncologia
L'Hospitalet de Llobregat, 08908
Hospital Universitario 12 De Octubre
Madrid, 28041
Clinica Universidad de Navarra - Clinica Universitaria De Navarra
Pamplona
Switzerland4 sites
University Hospital of Geneva
Geneva
Centre Hospitalier Universitaire Vaudois
Lausanne
Kantonsspital
Sankt Gallen
UniversitaetsSpital
Zurich
Austria3 sites
Innsbruck Universitaetsklinik
Innsbruck, 6020
Kepler University Hospital
Linz, 4020
Medical University Vienna - General Hospital AKH
Vienna, 1090
United Kingdom3 sites
NHS Lothian - Western General Hospital
Edinburgh, EH4 2XU
Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital
London
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
Sheffield, S10 2SJ
Denmark2 sites
Aarhus University Hospitals - Aarhus University Hospital
Aarhus, 8000
University Hospitals Copenhagen - Rigshospitalet
Copenhagen, 2100
About this study
Official title: A Phase III Trial of Marizomib in Combination With Standard Temozolomide-based Radiochemotherapy Versus Standard Temozolomide-based Radiochemotherapy Alone in Patients With Newly Diagnosed Glioblastoma
The standard of care for newly diagnosed glioblastoma includes surgery, involved-field radiotherapy, and concomitant and six cycles of maintenance temozolomide chemotherapy, however the prognosis remains dismal. Marizomib has been tested in patients with newly diagnosed and recurrent glioblastoma in phase I and phase II studies. In patients with recurrent glioblastoma, marizomib was administered as a single agent or in combination with bevacizumab (NCT02330562). Based on encouraging observations, a phase I/II trial of marizomib in combination with Temozolomide+Radiotherapy(TMZ/RT) followed by Temozolomide (TMZ) in newly diagnosed glioblastoma has been launched (NCT02903069) which explores safety and tolerability of this triple combination and which shall help to determine the dose for further clinical trials in glioblastoma. In this context, given that marizomib has been established as a safe addition to the standard TMZ/RT -->TMZ, a phase III study is considered essential to establishing its impact on overall survival.
- Conditions
- Newly Diagnosed Glioblastoma
- Being tested
- Marizomib, Temozolomide, radiotherapy
- Keywords
- Marizomib, Temozolomide, Glioblastoma, Phase III
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MarizomibDrug
Intravenous administration of Marizomib
TemozolomideDrug
Also called TMZ
Oral Administration of Temozolomide
radiotherapyRadiation
Also called RT
60 Gy in 30 fractions over 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib Receives: Drug: Marizomib; Drug: Temozolomide; Radiation: radiotherapy |
| Standard Arm | Active comparator | Radiotherapy + Temozolomide followed by adjuvant Temozolomide Receives: Drug: Temozolomide; Radiation: radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall Survival (OS): OS is defined as the number of days from date of randomization to the date of death due to any cause. If a patient has not died, the data will be censored at the last date documented to be alive.
Measured: From the date of randomization up to the date of death, assessed up to 49 months
Secondary outcomes (3)
Progression Free Survival (PFS)
PFS is defined as the number of days from date of randomization to the date of earliest disease progression based on Response Assessment in Neuro-Oncology criteria (by investigator) or to the date of death due to any cause, if disease progression does not occur. Patients for whom neither death nor progression have been documented were censored on the date of the last radiological assessment that the patient was progression-free. If a patient with no post-baseline radiological assessment then the data were censored at the date of randomization. Patients with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where the patient was documented to be progression free. Patients who received new anti-cancer therapy or cancer-related surgery prior to progression or death were not censored at the last assessment where the patient was documented as progression free prior to the new therapy.
Measured: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first, assessed up to 49 months
Health-related Quality of Life (HRQol)
HRQoL was assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3. The primary HRQol score is Physical Functioning. It is reported at week 16 during the Temozolomide (TMZ) maintenance phase. Physical functioning score is ranging 0 to 100. A large scores indicate a good physical functioning. A negative difference indicates a worsening physical functioning.
Measured: From randomization until progression or death which ever occurs first, reported at week 16 by the mean difference from baseline assessment.
Mini Mental State Examination (MMSE)
MMSE is a brief, standardized tool to grade patients' neurocognitive function. It is an 11-question measure that tests five areas of neurocognitive function: orientation, registration, attention and calculation, recall, and language. A large MMSE score indicates a good cognitive functioning. The maximum MMSE score is 30 which corresponds to the best neurocognitive function and minimum MMSE score is 0 the worst neurocognitive function.The patient's neurocognitive function are considered 'impaired' if MMSE is 26 or less and 'normal' if it is 27 or more. MMSE has been validated and extensively used in both clinical practice and research. It is reported at week 16 during the Temozolomide (TMZ) maintenance phase. A negative difference indicates a worsening cognitive functioning. Difference range reported in the data table is min -19 and max 10. The mean difference is reported with 95% confidence interval (CI). A CI which excludes 0 indicates a significant mean MMSE score change.
Measured: From the date of randomization until end of treatment. It is reported at week 16 by the mean difference from baseline assessment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start26 Jul 2018
- Primary completion23 Aug 2022
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Newly Diagnosed 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
- 749 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Celgene, Canadian Cancer Trials Group
- Responsible party
- Sponsor
- Investigators
- Patrick Roth, Principal investigator, EORTC Study Coordinator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03345095
- Sponsor's protocol ID
- EORTC-BTG-1709
- Acronym
- MIRAGE
- Status last verified
- Jun 2025
- First submitted
- 7 Nov 2017
- Last updated
- 1 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No