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

NCT03345095 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: EORTC-BTG-1709
• Study Type: interventional
• Target: 749
• Locations: 12 countries
• Sites: 82

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

Keywords

Marizomib; Temozolomide; Glioblastoma; Phase III

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• Health-related Quality of Life (HRQol)

  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)

  From the date of randomization until end of treatment. It is reported at week 16 by the mean difference from baseline assessment.

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib

Drug: Marizomib; Drug: Temozolomide; Radiation: radiotherapy

Standard Arm

ACTIVE COMPARATOR

Radiotherapy + Temozolomide followed by adjuvant Temozolomide

Drug: Temozolomide; Radiation: radiotherapy

Interventions

Marizomib DRUG

Intravenous administration of Marizomib

Experimental Arm

Temozolomide DRUG

Oral Administration of Temozolomide

Also known as: TMZ

Experimental Arm; Standard Arm

radiotherapy RADIATION

60 Gy in 30 fractions over 6 weeks

Also known as: RT

Experimental Arm; Standard Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Celgene: collaborator
• Canadian Cancer Trials Group: collaborator

Study Sites (82)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of California at Irvine

Orange, California, 92868, United States

Location

University of California

San Francisco, California, 94143-0372, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

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

Hershey, Pennsylvania, 17033, United States

Location

Innsbruck Universitaetsklinik

Innsbruck, 6020, Austria

Location

Kepler University Hospital

Linz, 4020, Austria

Location

Medical University Vienna - General Hospital AKH

Vienna, 1090, Austria

Location

Onze Lieve Vrouw Ziekenhuis

Aalst, 9300, Belgium

Location

GasthuisZusters Antwerpen - Sint-Augustinus

Antwerp, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

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

Charleroi, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

C.H.U. Sart-Tilman

Liège, Belgium

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

London Regional Cancer Center

London, Ontario, N6A 4L6, Canada

Location

Ottawa Health Research Institute

Ottawa, Ontario, K1Y 4K7, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, Canada

Location

Tom Baker Cancer Centre

Calgary, AB T2N 4N2, Canada

Location

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

Greater Sudbury, Canada

Location

QEII Health Sciences Centre-Capital District Health Authority

Halifax, CA B3H 1V7, Canada

Location

Hamilton Health Sciences, Juravinski Cancer Centre

Hamilton, Canada

Location

Kingston Health Sciences Centre

Kingston, CA K7L 2V7, Canada

Location

Montreal Neurological Institute and Hospital McGill University

Montreal, H3A 2B4, Canada

Location

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

Montreal, Canada

Location

Hopital Du Sacre-Coeur De Montreal

Montreal, Canada

Location

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

Québec, Canada

Location

Allan Blair Cancer Centre

Regina, Canada

Location

Sault Area Hospital

Sault Ste. Marie, Canada

Location

Odette Cancer Centre - Sunnybrook Health Sciences Centre

Toronto, Canada

Location

University Health Network - Oci / Princess Margaret Hospital

Toronto, Canada

Location

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Canada

Location

BC Cancer Agency

Vancouver, V5Z4E9, Canada

Location

Bcca - Vancouver Island Cancer Centre

Victoria, BC V8R 6V5, Canada

Location

Cancercare Manitoba

Winnipeg, Canada

Location

Aarhus University Hospitals - Aarhus University Hospital

Aarhus, 8000, Denmark

Location

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, 2100, Denmark

Location

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, Vendee, 85925, France

Location

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer

Bron, 69677, France

Location

CHRU de Lille

Lille, France

Location

Institut de Cancerologie de l'Ouest

Nantes, France

Location

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, France

Location

Gustave Roussy

Villejuif, France

Location

Universitaetsklinikum Bonn

Bonn, 53105, Germany

Location

Universitaetsklinik Erlangen-Neurologische Klinik

Erlangen, 91054, Germany

Location

Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie

Frankfurt, 60528, Germany

Location

UniversitaetsKlinikum Heidelberg - Head Hospital

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Leipzig-Klinik für Strahlentherapie und Radioonkologie

Leipzig, 04103, Germany

Location

Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center

Mainz, 55131, Germany

Location

UniversitaetsMedizin Mannheim

Mannheim, 68167, Germany

Location

Technische Universitaet Muenchen - Klinikum Rechts Der Isar

München, 81675, Germany

Location

Universitaetskliniken Regensburg

Regensburg, 93053, Germany

Location

Universitaetsklinikum Tuebingen- Crona Kliniken

Tübingen, 72076, Germany

Location

Catharina Ziekenhuis

Eindhoven, North Brabant, 5602, Netherlands

Location

Spaarne Gasthuis - Vrije Universiteit Medisch Centrum

Amsterdam, Netherlands

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202, Netherlands

Location

Radboud University Medical Center Nijmegen

Nijmegen, 6525, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Medisch Centrum Haaglanden - Westeinde

The Hague, 2501, Netherlands

Location

Universitair Medisch Centrum - Academisch Ziekenhuis

Utrecht, 3584, Netherlands

Location

Oslo University Hospital - Radiumhospitalet

Oslo, Norway

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Badalona, Spain

Location

Hospital Clinic Universitari de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala D'Oncologia

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

Location

Clinica Universidad de Navarra - Clinica Universitaria De Navarra

Pamplona, Spain

Location

University Hospital of Geneva

Geneva, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Kantonsspital

Sankt Gallen, Switzerland

Location

UniversitaetsSpital

Zurich, Switzerland

Location

NHS Lothian - Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital

London, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

marizomib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Dr. Thierry Gorlia
• Organization: EORTC

thierry.gorlia@eortc.org

+32 2 7741652

Study Officials

• Patrick Roth

  EORTC Study Coordinator

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 17, 2017
• Study Start: July 26, 2018
• Primary Completion: August 23, 2022
• Study Completion: June 30, 2023
• Last Updated: July 1, 2025
• Results First Posted: January 31, 2024

Record last verified: 2025-06

Locations

AU (3); GB (3); BE (7); ES (5); CH (4); DK (2); NL (9); NO (1); US (9); CA (23); FR (6); DE (10)