A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma
- Conditions
- Newly Diagnosed Glioblastoma
- Interventions
- Registration Number
- NCT03345095
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 749
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Histologically confirmed newly diagnosed glioblastoma (WHO grade IV)
-
Tumor resection (gross total or partial), or biopsy only
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Availability of formalin-fixed paraffin-embedded (FFPE) tumor block or 24 unstained slides for o6-methylguanine-DNA-methyltransferase (MGMT) analysis
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Patient must be eligible for standard TMZ/RT + TMZ
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Karnofsky performance score (KPS) ≥ 70
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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
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Stable or decreasing dose of steroids for at least 1 week prior to inclusion
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The patient has a life expectancy of at least 3 months
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Patient has undergone a brain MRI within 14 days of randomization but after intervention (resection or biopsy)
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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)
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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.
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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.
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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.
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Ability to take oral medication
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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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm Temozolomide Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib Experimental Arm radiotherapy Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib Standard Arm Temozolomide Radiotherapy + Temozolomide followed by adjuvant Temozolomide Standard Arm radiotherapy Radiotherapy + Temozolomide followed by adjuvant Temozolomide Experimental Arm Marizomib Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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.
Health-related Quality of Life (HRQol) From randomization until progression, assessed up to 49 months HRQoL will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3.
Mini Mental State Examination (MMSE) From the date of randomization until end of treatment, assessed up to 49 months 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.
Trial Locations
- Locations (81)
University of California
🇺🇸San Francisco, California, United States
Saint John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
University Hospital of Geneva
🇨🇭Geneva, Switzerland
University of Florida
🇺🇸Gainesville, Florida, United States
Medical University Vienna - General Hospital AKH
🇦🇹Vienna, Austria
Catharina Ziekenhuis
🇳🇱Eindhoven, North Brabant, Netherlands
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Kantonsspital
🇨🇭Saint Gallen, Switzerland
UniversitaetsSpital
🇨🇭Zürich, Switzerland
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States
University of California at Irvine
🇺🇸Orange, California, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Innsbruck Universitaetsklinik
🇦🇹Innsbruck, Austria
Kepler University Hospital
🇦🇹Linz, Austria
Onze Lieve Vrouw Ziekenhuis
🇧🇪Aalst, Belgium
GasthuisZusters Antwerpen - Sint-Augustinus
🇧🇪Antwerpen, Belgium
Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
🇧🇪Bruxelles, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
C.H.U. Sart-Tilman
🇧🇪Liège, Belgium
Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame
🇧🇪Charleroi, Belgium
London Regional Cancer Center
🇨🇦London, Ontario, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Windsor Regional Cancer Centre
🇨🇦Windsor, Ontario, 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
Montreal Neurological Institute and Hospital McGill University
🇨🇦Montréal, Canada
CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
🇨🇦Montréal, Canada
Hopital Du Sacre-Coeur De Montreal
🇨🇦Montréal, Canada
CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
🇨🇦Québec, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Canada
Sault Area Hospital
🇨🇦Sault Ste. Marie, Canada
Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital
🇨🇦Sudbury, Canada
Odette Cancer Centre - Sunnybrook Health Sciences Centre
🇨🇦Toronto, Canada
Centre hospitalier regional de Trois-Rivieres
🇨🇦Trois-Rivières, Canada
University Health Network - Oci / Princess Margaret Hospital
🇨🇦Toronto, Canada
BC Cancer Agency
🇨🇦Vancouver, Canada
Bcca - Vancouver Island Cancer Centre
🇨🇦Victoria, Canada
Aarhus University Hospitals - Aarhus University Hospital
🇩🇰Aarhus, Denmark
Cancercare Manitoba
🇨🇦Winnipeg, Canada
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
🇫🇷Bron, France
CHRU de Lille
🇫🇷Lille, France
Institut de Cancerologie de l'Ouest
🇫🇷Nantes, France
Centre Hospitalier Departemental Vendée
🇫🇷La Roche-sur-Yon, Vendee, France
Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
🇫🇷Paris, France
Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie
🇩🇪Frankfurt, Germany
Universitaetsklinik Erlangen-Neurologische Klinik
🇩🇪Erlangen, Germany
UniversitaetsKlinikum Heidelberg - Head Hospital
🇩🇪Heidelberg, Germany
Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
🇩🇪Leipzig, Germany
UniversitaetsMedizin Mannheim
🇩🇪Mannheim, Germany
Technische Universitaet Muenchen - Klinikum Rechts Der Isar
🇩🇪Muenchen, Germany
Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
Universitaetskliniken Regensburg
🇩🇪Regensburg, Germany
Universitaetsklinikum Tuebingen- Crona Kliniken
🇩🇪Tuebingen, Germany
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Medisch Centrum Haaglanden - Westeinde
🇳🇱Den Haag, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Universitair Medisch Centrum - Academisch Ziekenhuis
🇳🇱Utrecht, Netherlands
Radboud University Medical Center Nijmegen
🇳🇱Nijmegen, Netherlands
Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
🇪🇸Badalona, Spain
Oslo University Hospital - Radiumhospitalet
🇳🇴Oslo, Norway
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, Spain
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 Kingdom
University Hospitals Copenhagen - Rigshospitalet
🇩🇰Copenhagen, Denmark
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute
🇺🇸Hershey, Pennsylvania, United States
Ottawa Health Research Institute
🇨🇦Ottawa, Ontario, Canada
Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
🇩🇪Mainz, Germany