Clinical trial NCT00967330: A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-08-27
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From baseline to the end of the study (up to 4.5 years)
measure: Overall Survival (OS)
timeFrame: From baseline until death (up to 4.5 years)
measure: Percentage of Participants Who Discontinued
timeFrame: From baseline until death (up to 4.5 years)
measure: Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
timeFrame: 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
measure: Percentage of Participants With Response on FLAIR Imaging
timeFrame: At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
timeFrame: Baseline, Post-Baseline (up to Month 30)
measure: Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
timeFrame: Baseline, Post-Baseline (up to Month 30)
measure: Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
timeFrame: Baseline, Post-Baseline (up to Month 30)
measure: Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)
timeFrame: Baseline, Post-Baseline (up to Month 30)
measure: Percentage of Participants Who Received Corticosteroid for Glioblastoma
timeFrame: From baseline to Month 6
measure: Time to Treatment Failure
timeFrame: From baseline until end of study (up to 4.5 years)
Other outcomes:
Locations:
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Bonn
country: Germany
city: Chemnitz
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Erfurt
country: Germany
city: Erlangen
country: Germany
city: Frankfurt am Main
country: Germany
city: Freiburg
country: Germany
city: Göttingen
country: Germany
city: Idar-Oberstein
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Leipzig
country: Germany
city: Mannheim
country: Germany
city: Marburg
country: Germany
city: Muenchen
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Regensburg
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.