A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE)

June 26, 2025 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

749

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Innsbruck Universitaetsklinik
      • Linz, Austria, 4020
        • Kepler University Hospital
      • Vienna, Austria, 1090
        • Medical University Vienna - General Hospital AKH
  • Belgium
      • Aalst, Belgium, 9300
        • Onze Lieve Vrouw Ziekenhuis
      • Antwerpen, Belgium
        • GasthuisZusters Antwerpen - Sint-Augustinus
      • Bruxelles, Belgium
        • Cliniques universitaires Saint-Luc
      • Bruxelles, Belgium, 1070
        • Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
      • Charleroi, Belgium
        • Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame
      • Gent, Belgium, 9000
        • Universitair Ziekenhuis Gent
      • Liège, Belgium
        • C.H.U. Sart-Tilman
  • Canada
      • Abbotsford, Canada
        • BCCA - Abbotsford Centre
      • Calgary, Canada, AB T2N 4N2
        • Tom Baker Cancer Centre
      • Halifax, Canada, CA B3H 1V7
        • QEII Health Sciences Centre-Capital District Health Authority
      • Hamilton, Canada
        • Hamilton Health Sciences, Juravinski Cancer Centre
      • Kingston, Canada, CA K7L 2V7
        • Kingston Health Sciences Centre
      • Montréal, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital McGill University
      • Montréal, Canada
        • CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
      • Montréal, Canada
        • Hôpital du Sacré-Coeur de Montréal
      • Québec, Canada
        • CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
      • Regina, Canada
        • Allan Blair Cancer Centre
      • Sault Ste. Marie, Canada
        • Sault Area Hospital
      • Sudbury, Canada
        • Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital
      • Toronto, Canada
        • Odette Cancer Centre - Sunnybrook Health Sciences Centre
      • Toronto, Canada
        • University Health Network - Oci / Princess Margaret Hospital
      • Trois-Rivières, Canada
        • Centre hospitalier regional de Trois-Rivieres
      • Vancouver, Canada, V5Z4E9
        • BC Cancer Agency
      • Victoria, Canada, BC V8R 6V5
        • BCCA - Vancouver Island Cancer Centre
      • Winnipeg, Canada
        • CancerCare Manitoba
    • New Brunswick
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Saint John Regional Hospital
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Center
      • Ottawa, Ontario, Canada, K1Y 4K7
        • Ottawa Health Research Institute
      • Windsor, Ontario, Canada
        • Windsor Regional Cancer Centre
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Denmark
      • Aarhus, Denmark, 8000
        • Aarhus University Hospitals - Aarhus University Hospital
      • Copenhagen, Denmark, 2100
        • University Hospitals Copenhagen - Rigshospitalet
  • France
      • Bron, France, 69677
        • CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
      • Lille, France
        • CHRU de Lille
      • Nantes, France
        • Institut de Cancérologie de l'Ouest
      • Paris, France
        • Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
      • Villejuif, France
        • Gustave Roussy
    • Vendee
      • La Roche-sur-Yon, Vendee, France, 85925
        • Centre Hospitalier Départemental Vendée
  • Germany
      • Bonn, Germany, 53105
        • Universitaetsklinikum Bonn
      • Erlangen, Germany, 91054
        • Universitaetsklinik Erlangen-Neurologische Klinik
      • Frankfurt, Germany, 60528
        • Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie
      • Heidelberg, Germany, 69120
        • UniversitaetsKlinikum Heidelberg - Head Hospital
      • Leipzig, Germany, 04103
        • Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
      • Mainz, Germany, 55131
        • Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
      • Mannheim, Germany, 68167
        • UniversitaetsMedizin Mannheim
      • Muenchen, Germany, 81675
        • Technische Universitaet Muenchen - Klinikum Rechts Der Isar
      • Regensburg, Germany, 93053
        • Universitaetskliniken Regensburg
      • Tuebingen, Germany, 72076
        • Universitaetsklinikum Tuebingen- Crona Kliniken
  • Netherlands
      • Amsterdam, Netherlands
        • Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
      • Amsterdam, Netherlands
        • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
      • Den Haag, Netherlands, 2501
        • Medisch Centrum Haaglanden - Westeinde
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Maastricht, Netherlands, 6202
        • Academisch Ziekenhuis Maastricht
      • Nijmegen, Netherlands, 6525
        • Radboud University Medical Center Nijmegen
      • Rotterdam, Netherlands
        • Erasmus MC
      • Utrecht, Netherlands, 3584
        • Universitair Medisch Centrum - Academisch Ziekenhuis
    • North Brabant
      • Eindhoven, North Brabant, Netherlands, 5602
        • Catharina Ziekenhuis
  • Norway
      • Oslo, Norway
        • Oslo University Hospital - Radiumhospitalet
  • Spain
      • Badalona, Spain
        • Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
      • Barcelona, Spain, 08036
        • Hospital Clinic Universitari de Barcelona
      • L'Hospitalet De Llobregat, Spain, 08908
        • Institut Catala D'oncologia
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Pamplona, Spain
        • Clinica Universidad de Navarra - Clinica Universitaria De Navarra
  • Switzerland
      • Geneva, Switzerland
        • University Hospital of Geneva
      • Lausanne, Switzerland
        • Centre Hospitalier Universitaire Vaudois
      • Saint Gallen, Switzerland
        • Kantonsspital
      • Zürich, Switzerland
        • UniversitaetsSpital
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • NHS Lothian - Western General Hospital
      • London, United Kingdom
        • Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital
      • Sheffield, United Kingdom, S10 2SJ
        • Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Scottsdale
    • California
      • Orange, California, United States, 92868
        • University of California at Irvine
      • San Francisco, California, United States, 94143-0372
        • University of California
      • Santa Monica, California, United States, 90404
        • John Wayne Cancer Institute
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Arm
Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib
Drug: Marizomib
Intravenous administration of Marizomib
Other Names:
  • MRZ
Drug: Temozolomide
Oral Administration of Temozolomide
Other Names:
  • TMZ
Radiation: radiotherapy
60 Gy in 30 fractions over 6 weeks
Other Names:
  • RT
Active Comparator: Standard Arm
Radiotherapy + Temozolomide followed by adjuvant Temozolomide
Drug: Temozolomide
Oral Administration of Temozolomide
Other Names:
  • TMZ
Radiation: radiotherapy
60 Gy in 30 fractions over 6 weeks
Other Names:
  • RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the date of randomization up to the date of death, assessed up to 49 months
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.
From the date of randomization up to the date of death, assessed up to 49 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 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
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.
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)
Time Frame: From randomization until progression or death which ever occurs first, reported at week 16 by the mean difference from baseline assessment.
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.
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)
Time Frame: From the date of randomization until end of treatment. It is reported at week 16 by the mean difference from baseline assessment.
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.
From the date of randomization until end of treatment. It is reported at week 16 by the mean difference from baseline assessment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Celgene
Canadian Cancer Trials Group

Investigators

  • Principal Investigator: Patrick Roth, EORTC Study Coordinator

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2018

Primary Completion (Actual)

August 23, 2022

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

November 7, 2017

First Submitted That Met QC Criteria

November 14, 2017

First Posted (Actual)

November 17, 2017

Study Record Updates

Last Update Posted (Estimated)

July 1, 2025

Last Update Submitted That Met QC Criteria

June 26, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-BTG-1709

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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