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

• ClinicalTrials.gov Identifier: NCT03345095
• Recruitment Status: Active, not recruiting
• First Posted: November 17, 2017
• Last Update Posted: October 6, 2020
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Celgene; Canadian Cancer Trials Group
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: November 7, 2017
• First Posted Date: November 17, 2017
• Last Update Posted Date: October 6, 2020
• Actual Study Start Date: July 26, 2018
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2017): Overall Survival (OS) [ Time Frame: From the date of randomization up to the date of death, assessed up to 49 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2017)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Newly Diagnosed Glioblastoma

Intervention

• 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

Study Arms

• Experimental: Experimental Arm
  Radiotherapy + Temozolomide + Marizomib followed by adjuvant Temozolomide + Marizomib
  Interventions:

  • Drug: Marizomib
  • Drug: Temozolomide
  • Radiation: radiotherapy
• Active Comparator: Standard Arm
  Radiotherapy + Temozolomide followed by adjuvant Temozolomide
  Interventions:

  • Drug: Temozolomide
  • Radiation: radiotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 5, 2020): 749
• Original Estimated Enrollment (submitted: November 14, 2017): 750
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Denmark, France, Germany, Netherlands, Norway, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT03345095
• Other Study ID Numbers: EORTC-BTG-1709
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Original Responsible Party: Same as current
• Current Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Original Study Sponsor: Same as current

Collaborators

• Celgene
• Canadian Cancer Trials Group

Investigators

• Principal Investigator: Patrick Roth; EORTC Study Coordinator

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: October 2020