Clinical trial NCT03345095: A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Newly Diagnosed Glioblastoma
Keywords: Marizomib
Temozolomide
Glioblastoma
Phase III
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Celgene
name: Canadian Cancer Trials Group
First posted: 2017-11-17
Enrollment: 749
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization up to the date of death, assessed up to 49 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Health-related Quality of Life (HRQol)
timeFrame: From randomization until progression, assessed up to 49 months
measure: Mini Mental State Examination (MMSE)
timeFrame: From the date of randomization until end of treatment, assessed up to 49 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Orange
country: United States
facility: University of California at Irvine
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute
state: Pennsylvania
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Linz
country: Austria
facility: Kepler University Hospital
city: Vienna
country: Austria
facility: Medical University Vienna - General Hospital AKH
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis
city: Antwerpen
country: Belgium
facility: GasthuisZusters Antwerpen - Sint-Augustinus
city: Bruxelles
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liège
country: Belgium
facility: C.H.U. Sart-Tilman
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: London
country: Canada
facility: London Regional Cancer Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
state: Quebec
city: Abbotsford
country: Canada
facility: BCCA - Abbotsford Centre
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: Halifax
country: Canada
facility: QEII Health Sciences Centre-Capital District Health Authority
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, Juravinski Cancer Centre
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital McGill University
city: Montréal
country: Canada
facility: CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
city: Montréal
country: Canada
facility: Hopital Du Sacre-Coeur De Montreal
city: Québec
country: Canada
facility: CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
city: Sault Ste. Marie
country: Canada
facility: Sault Area Hospital
city: Sudbury
country: Canada
facility: Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital
city: Toronto
country: Canada
facility: Odette Cancer Centre - Sunnybrook Health Sciences Centre
city: Toronto
country: Canada
facility: University Health Network - Oci / Princess Margaret Hospital
city: Trois-Rivières
country: Canada
facility: Centre hospitalier regional de Trois-Rivieres
city: Vancouver
country: Canada
facility: BC Cancer Agency
city: Victoria
country: Canada
facility: Bcca - Vancouver Island Cancer Centre
city: Winnipeg
country: Canada
facility: Cancercare Manitoba
city: Aarhus
country: Denmark
facility: Aarhus University Hospitals - Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: University Hospitals Copenhagen - Rigshospitalet
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Departemental Vendée
state: Vendee
city: Bron
country: France
facility: CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
city: Lille
country: France
facility: CHRU de Lille
city: Nantes
country: France
facility: Institut de Cancerologie de l'Ouest
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
city: Villejuif
country: France
facility: Gustave Roussy
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Erlangen
country: Germany
facility: Universitaetsklinik Erlangen-Neurologische Klinik
city: Frankfurt
country: Germany
facility: Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie
city: Heidelberg
country: Germany
facility: UniversitaetsKlinikum Heidelberg - Head Hospital
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
city: Mannheim
country: Germany
facility: UniversitaetsMedizin Mannheim
city: Muenchen
country: Germany
facility: Technische Universitaet Muenchen - Klinikum Rechts Der Isar
city: Regensburg
country: Germany
facility: Universitaetskliniken Regensburg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen- Crona Kliniken
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: North Brabant
city: Amsterdam
country: Netherlands
facility: Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
city: Den Haag
country: Netherlands
facility: Medisch Centrum Haaglanden - Westeinde
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum - Academisch Ziekenhuis
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari de Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Institut Catala D'Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Clinica Universitaria De Navarra
city: Geneva
country: Switzerland
facility: University Hospital of Geneva
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Saint Gallen
country: Switzerland
facility: Kantonsspital
city: Zürich
country: Switzerland
facility: UniversitaetsSpital
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
Study officials:
affiliation: EORTC Study Coordinator
name: Patrick Roth
role: PRINCIPAL_INVESTIGATOR
References: