NCT00967330

Brief Summary

This 2 arm study will compare the effect of Avastin + irinotecan versus temozolomide, in combination with conventional involved field radiotherapy, in patients with newly diagnosed glioblastoma and a non-methylated MGMT promoter. Patients will be randomized 3:1 to receive Avastin 10mg/kg iv every 2 weeks + irinotecan 125mg/m2 iv every 2 weeks, or temozolomide 75mg/m2 po daily during radiotherapy followed by 6 cycles of temozolomide 150-200mg/m2 po daily on days 1-5 of each 4 week cycle. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
182

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2010

Typical duration for phase_2

Geographic Reach
1 country

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 16, 2009

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 27, 2009

Completed
9 months until next milestone

Study Start

First participant enrolled

June 1, 2010

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

November 20, 2015

Completed
Last Updated

November 20, 2015

Status Verified

October 1, 2015

Enrollment Period

4.3 years

First QC Date

June 16, 2009

Results QC Date

October 20, 2015

Last Update Submit

October 20, 2015

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months

    Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased. Percentage of participants achieving PFS without disease progression or death was reported.

    6 months

Secondary Outcomes (11)

  • Progression-Free Survival (PFS)

    From baseline to the end of the study (up to 4.5 years)

  • Overall Survival (OS)

    From baseline until death (up to 4.5 years)

  • Percentage of Participants Who Discontinued

    From baseline until death (up to 4.5 years)

  • Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)

    4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6

  • Percentage of Participants With Response on FLAIR Imaging

    At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)

  • +6 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL
Drug: bevacizumab [Avastin]Drug: irinotecan

2

ACTIVE COMPARATOR
Drug: temozolomide

Interventions

bevacizumab [Avastin]DRUG

10mg/kg iv every 2 weeks

1
irinotecanDRUG

125mg/m2 iv every 2 weeks

1
temozolomideDRUG

75mg/m2 po daily during radiotherapy, followed by 150-200mg/m2/day po on days 1-5 of each 6x4 week cycle of adjuvant therapy

2

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • adult patients, 18-70 years of age;
  • glioblastoma, confirmed histologically;
  • no previous chemotherapy or radiotherapy for glioblastoma;
  • non-methylated MGMT promoter in the tumor.

You may not qualify if:

  • prior systemic treatment for glioblastoma multiforme;
  • prior treatment with Avastin;
  • significant cardiovascular disease;
  • other active malignant disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Unknown Facility

Aachen, 52074, Germany

Location

Unknown Facility

Berlin, 13353, Germany

Location

Unknown Facility

Bochum, 44892, Germany

Location

Unknown Facility

Bonn, 53127, Germany

Location

Unknown Facility

Chemnitz, 09113, Germany

Location

Unknown Facility

Cologne, 50937, Germany

Location

Unknown Facility

Dresden, 01307, Germany

Location

Unknown Facility

Düsseldorf, 40225, Germany

Location

Unknown Facility

Erfurt, 99089, Germany

Location

Unknown Facility

Erlangen, 91054, Germany

Location

Unknown Facility

Frankfurt am Main, 60528, Germany

Location

Unknown Facility

Freiburg im Breisgau, 79106, Germany

Location

Unknown Facility

Göttingen, 37075, Germany

Location

Unknown Facility

Idar-Oberstein, 55743, Germany

Location

Unknown Facility

Kiel, 24105, Germany

Location

Unknown Facility

Leipzig, 04103, Germany

Location

Unknown Facility

Mannheim, 68167, Germany

Location

Unknown Facility

Marburg, 35043, Germany

Location

Unknown Facility

München, 81377, Germany

Location

Unknown Facility

München, 81675, Germany

Location

Unknown Facility

Münster, 48149, Germany

Location

Unknown Facility

Regensburg, 93053, Germany

Location

Unknown Facility

Tübingen, 72076, Germany

Location

Unknown Facility

Ulm, 89081, Germany

Location

Related Publications (2)

  • Schafer N, Proescholdt M, Steinbach JP, Weyerbrock A, Hau P, Grauer O, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Grau S, Hanel M, Schnell O, Krex D, Vajkoczy P, Tabatabai G, Mack F, Schaub C, Tzaridis T, Niessen M, Kebir S, Leutgeb B, Urbach H, Belka C, Stummer W, Glas M, Herrlinger U. Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma. Neuro Oncol. 2018 Jun 18;20(7):975-985. doi: 10.1093/neuonc/nox204.

    PMID: 29121274DERIVED

  • Herrlinger U, Schafer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hanel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tuttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016 May 10;34(14):1611-9. doi: 10.1200/JCO.2015.63.4691. Epub 2016 Mar 14.

    PMID: 26976423DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

BevacizumabIrinotecanTemozolomide

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCamptothecinAlkaloidsHeterocyclic CompoundsDacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-Ring

Limitations and Caveats

Data for time to treatment failure were not collected as this outcome was removed as per changes in planned analysis.

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche
genentech@druginfo.com
800 821-8590

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 16, 2009

First Posted

August 27, 2009

Study Start

June 1, 2010

Primary Completion

September 1, 2014

Study Completion

September 1, 2014

Last Updated

November 20, 2015

Results First Posted

November 20, 2015

Record last verified: 2015-10

Locations

DE(24)