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

NCT ID: NCT03345095

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 749 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-26
• Study Completion Date: 2023-06-30

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.

Conditions

Newly Diagnosed Glioblastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm

Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib

Group Type: EXPERIMENTAL

Marizomib

Intervention Type: DRUG

Intravenous administration of Marizomib

Temozolomide

Intervention Type: DRUG

Oral Administration of Temozolomide

radiotherapy

Intervention Type: RADIATION

60 Gy in 30 fractions over 6 weeks

Standard Arm

Radiotherapy + Temozolomide followed by adjuvant Temozolomide

Group Type: ACTIVE_COMPARATOR

Temozolomide

Intervention Type: DRUG

Oral Administration of Temozolomide

radiotherapy

Intervention Type: RADIATION

60 Gy in 30 fractions over 6 weeks

Interventions

Marizomib

Intravenous administration of Marizomib

Intervention Type: DRUG

Temozolomide

Oral Administration of Temozolomide

Intervention Type: DRUG

radiotherapy

60 Gy in 30 fractions over 6 weeks

Intervention Type: RADIATION

Other Intervention Names

TMZ; RT

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Roth

Role: PRINCIPAL_INVESTIGATOR

EORTC Study Coordinator

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

University of California at Irvine

Orange, California, United States

University of California

San Francisco, California, United States

John Wayne Cancer Institute

Santa Monica, California, United States

University of Florida

Gainesville, Florida, United States

Mayo Clinic

Jacksonville, Florida, United States

Mayo Clinic

Rochester, Minnesota, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Penn State College of Medicine, Hershey Medical Center-Penn State Neuroscience Institute

Hershey, Pennsylvania, United States

Innsbruck Universitaetsklinik

Innsbruck, , Austria

Kepler University Hospital

Linz, , Austria

Medical University Vienna - General Hospital AKH

Vienna, , Austria

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

GasthuisZusters Antwerpen - Sint-Augustinus

Antwerp, , Belgium

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame

Charleroi, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

C.H.U. Sart-Tilman

Liège, , Belgium

Saint John Regional Hospital

Saint John, New Brunswick, Canada

London Regional Cancer Center

London, Ontario, Canada

Ottawa Health Research Institute

Ottawa, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, Canada

BCCA - Abbotsford Centre

Abbotsford, , Canada

Tom Baker Cancer Centre

Calgary, , Canada

Regional Cancer Program of Hopital Reg. de Sudbury Reg. Hospital

Greater Sudbury, , 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

Montreal, , Canada

CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame

Montreal, , Canada

Hopital Du Sacre-Coeur De Montreal

Montreal, , Canada

CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)

Québec, , Canada

Allan Blair Cancer Centre

Regina, , Canada

Sault Area Hospital

Sault Ste. Marie, , 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

Cancercare Manitoba

Winnipeg, , Canada

Aarhus University Hospitals - Aarhus University Hospital

Aarhus, , Denmark

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, , Denmark

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, Vendee, France

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer

Bron, , 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, , France

Universitaetsklinikum Bonn

Bonn, , Germany

Universitaetsklinik Erlangen-Neurologische Klinik

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

München, , Germany

Universitaetskliniken Regensburg

Regensburg, , Germany

Universitaetsklinikum Tuebingen- Crona Kliniken

Tübingen, , Germany

Catharina Ziekenhuis

Eindhoven, North Brabant, Netherlands

Spaarne Gasthuis - Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Radboud University Medical Center Nijmegen

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Medisch Centrum Haaglanden - Westeinde

The Hague, , Netherlands

Universitair Medisch Centrum - Academisch Ziekenhuis

Utrecht, , Netherlands

Oslo University Hospital - Radiumhospitalet

Oslo, , Norway

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, , Spain

University Hospital of Geneva

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital

Sankt Gallen, , Switzerland

UniversitaetsSpital

Zurich, , Switzerland

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

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

EORTC-BTG-1709

Identifier Type: -

Identifier Source: org_study_id