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

Newly Diagnosed Glioblastoma Clinical Trial

— MIRAGE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03345095
• Other study ID #: EORTC-BTG-1709
• Status: Completed
• Phase: Phase 3
• Start date: July 26, 2018
• Est. completion date: June 30, 2023

Study information

• Verified date: February 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 749
• Est. completion date: June 30, 2023
• Est. primary completion date: August 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Newly Diagnosed Glioblastoma

Intervention

Drug:
• Marizomib
Intravenous administration of Marizomib
• Temozolomide
Oral Administration of Temozolomide

Radiation:
• radiotherapy
60 Gy in 30 fractions over 6 weeks

Locations

Country	Name	City	State
Austria	Innsbruck Universitaetsklinik	Innsbruck
Austria	Kepler University Hospital	Linz
Austria	Medical University Vienna - General Hospital AKH	Vienna
Belgium	Onze Lieve Vrouw Ziekenhuis	Aalst
Belgium	GasthuisZusters Antwerpen - Sint-Augustinus	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme	Bruxelles
Belgium	Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame	Charleroi
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	C.H.U. Sart-Tilman	Liège
Canada	BCCA - Abbotsford Centre	Abbotsford
Canada	Tom Baker Cancer Centre	Calgary
Canada	QEII Health Sciences Centre-Capital District Health Authority	Halifax
Canada	Hamilton Health Sciences, Juravinski Cancer Centre	Hamilton
Canada	Kingston Health Sciences Centre	Kingston
Canada	London Regional Cancer Center	London	Ontario
Canada	CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame	Montréal
Canada	Hopital Du Sacre-Coeur De Montreal	Montréal
Canada	Montreal Neurological Institute and Hospital McGill University	Montréal
Canada	Ottawa Health Research Institute	Ottawa	Ontario
Canada	CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)	Québec
Canada	Allan Blair Cancer Centre	Regina
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Sault Area Hospital	Sault Ste. Marie
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital	Sudbury
Canada	Odette Cancer Centre - Sunnybrook Health Sciences Centre	Toronto
Canada	University Health Network - Oci / Princess Margaret Hospital	Toronto
Canada	Centre hospitalier regional de Trois-Rivieres	Trois-Rivières
Canada	BC Cancer Agency	Vancouver
Canada	Bcca - Vancouver Island Cancer Centre	Victoria
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	Cancercare Manitoba	Winnipeg
Denmark	Aarhus University Hospitals - Aarhus University Hospital (440)	Aarhus
Denmark	University Hospitals Copenhagen - Rigshospitalet	Copenhagen
France	CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer	Bron
France	Centre Hospitalier Departemental Vendée	La Roche-sur-Yon	Vendee
France	CHRU de Lille	Lille
France	Institut de Cancerologie de l'Ouest	Nantes
France	Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere	Paris
France	Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Universitaetsklinik Erlangen-Neurologische Klinik (3031)	Erlangen
Germany	Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie	Frankfurt
Germany	UniversitaetsKlinikum Heidelberg - Head Hospital	Heidelberg
Germany	Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie	Leipzig
Germany	Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center	Mainz
Germany	UniversitaetsMedizin Mannheim	Mannheim
Germany	Technische Universitaet Muenchen - Klinikum Rechts Der Isar	Muenchen
Germany	Universitaetskliniken Regensburg	Regensburg
Germany	Universitaetsklinikum Tuebingen- Crona Kliniken	Tuebingen
Netherlands	Spaarne Gasthuis - Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis	Amsterdam
Netherlands	Medisch Centrum Haaglanden - Westeinde	Den Haag
Netherlands	Catharina Ziekenhuis	Eindhoven	North Brabant
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Radboud University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum - Academisch Ziekenhuis	Utrecht
Norway	Oslo University Hospital - Radiumhospitalet	Oslo
Spain	Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)	Badalona
Spain	Hospital Clinic Universitari de Barcelona	Barcelona
Spain	Institut Catala D'Oncologia	L'Hospitalet De Llobregat
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Clinica Universidad de Navarra - Clinica Universitaria De Navarra	Pamplona
Switzerland	University Hospital of Geneva	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital	Saint Gallen
Switzerland	UniversitaetsSpital	Zürich
United Kingdom	NHS Lothian - Western General Hospital	Edinburgh
United Kingdom	Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital	Sheffield
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute	Hershey	Pennsylvania
United States	Mayo Clinic	Jacksonville	Florida
United States	University of California at Irvine	Orange	California
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California	San Francisco	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Canadian Cancer Trials Group, Celgene

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Netherlands,  Norway,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the date of randomization up to the date of death, assessed up to 49 months
Secondary	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.	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
Secondary	Health-related Quality of Life (HRQol)	HRQoL will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3.	From randomization until progression, assessed up to 49 months
Secondary	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. The maximum score is 30 which corresponds to the best neurocognitive function. The patient's neurocognitive function are considered 'impaired' if the MMSE score is 26 or less and 'normal' if it is 27 or more. Since its creation in 1975, MMSE has been validated and extensively used in both clinical practice and research.	From the date of randomization until end of treatment, assessed up to 49 months