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

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ClinicalTrials.gov Identifier: NCT03345095
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : June 17, 2019
Sponsor:
Collaborators:
Celgene
Canadian Cancer Trials Group
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

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 TMZ/RT -->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.

Condition or disease Intervention/treatment Phase
Newly Diagnosed Glioblastoma Drug: Marizomib Drug: Temozolomide Radiation: radiotherapy Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 26, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental Arm
Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib
Drug: Marizomib
Intravenous administration of Marizomib
Other Name: MRZ

Drug: Temozolomide
Oral Administration of Temozolomide
Other Name: TMZ

Radiation: radiotherapy
60 Gy in 30 fractions over 6 weeks
Other Name: RT

Active Comparator: Standard Arm
Radiotherapy + Temozolomide followed by adjuvant Temozolomide
Drug: Temozolomide
Oral Administration of Temozolomide
Other Name: TMZ

Radiation: radiotherapy
60 Gy in 30 fractions over 6 weeks
Other Name: RT




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From the date of randomization up to the date of death, assessed up to 49 months ]

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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 ]
  2. Health-related Quality of life (HRQol) [ Time Frame: From randomization until progression, assessed up to 49 months ]
    HRQoL will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3.

  3. Mini Mental State Examination (MMSE) [ Time Frame: From the date of randomization until end of treatment, assessed up to 49 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed newly diagnosed glioblastoma (WHO grade IV)
  • Tumor resection (gross total or partial), or biopsy only
  • Availability of FFPE tumor block or 24 unstained slides for 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:

    • WBC ≥ 3×10*9/L
    • ANC ≥ 1.5×10*9/L
    • Platelet count of ≥ 100×10*9/L independent of transfusion
    • Hemoglobin ≥ 10 g/dl
    • Total Bilirubin ≤ 1.5 ULN
    • ALT, 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 ICH/GCP, and national/local regulations.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03345095


Contacts
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Contact: EORTC +3227741611 eortc@eortc.org

  Show 55 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Celgene
Canadian Cancer Trials Group
Investigators
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Principal Investigator: Patrick Roth EORTC Study Coordinator

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT03345095     History of Changes
Other Study ID Numbers: EORTC-BTG-1709
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
Marizomib
Temozolomide
Glioblastoma
Phase III
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents