A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00967330
First received: June 16, 2009
Last updated: October 20, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Glioblastoma Multiforme
Drug: bevacizumab [Avastin]
Drug: irinotecan
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From baseline to the end of the study (up to 4.5 years) ] [ Designated as safety issue: No ]
    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% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased. PFS was estimated using Kaplan-Meier method.

  • Overall Survival (OS) [ Time Frame: From baseline until death (up to 4.5 years) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization to death from any cause. OS was estimated using Kaplan-Meier method.

  • Percentage of Participants Who Discontinued [ Time Frame: From baseline until death (up to 4.5 years) ] [ Designated as safety issue: No ]
    Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm. Percentage of participant with individual discontinuation reason are reported. CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events . Other reason refers to any other reason than the specified ones.

  • Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) [ Time Frame: 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6 ] [ Designated as safety issue: No ]
    BOR was defined as the best response observed for a participant during assessment. Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported. Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved.

  • Percentage of Participants With Response on FLAIR Imaging [ Time Frame: At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years) ] [ Designated as safety issue: No ]

    FLAIR lesions were determined as "stable", "progressive" or "decreased". FLAIR lesions was determined as "progressive" only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population.

    Dis.=Discontinuation.


  • 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) [ Time Frame: Baseline, Post-Baseline (up to Month 30) ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms. The change in global health status was determined to be the difference in values at baseline and each specific visit. The term ''baseline'' refers to the time of randomization to the maintenance phase.

  • Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) [ Time Frame: Baseline, Post-Baseline (up to Month 30) ] [ Designated as safety issue: No ]
    EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g. headaches and seizures), treatment toxicities (e.g. hair loss) and future uncertainty. All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

  • Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) [ Time Frame: Baseline, Post-Baseline (up to Month 30) ] [ Designated as safety issue: No ]
    The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability. Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function.

  • Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30) [ Time Frame: Baseline, Post-Baseline (up to Month 30) ] [ Designated as safety issue: No ]
    KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Deterioration in KPS was defined as decrease of 20 or more points in KPS score.

  • Percentage of Participants Who Received Corticosteroid for Glioblastoma [ Time Frame: From baseline to Month 6 ] [ Designated as safety issue: No ]
    Participants used corticosteroids for the glioblastoma condition. Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.

  • Time to Treatment Failure [ Time Frame: From baseline until end of study (up to 4.5 years) ] [ Designated as safety issue: No ]

Enrollment: 182
Study Start Date: June 2010
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
10mg/kg iv every 2 weeks
Drug: irinotecan
125mg/m2 iv every 2 weeks
Active Comparator: 2 Drug: temozolomide
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967330

Locations
Germany
Aachen, Germany, 52074
Berlin, Germany, 13353
Bochum, Germany, 44892
Bonn, Germany, 53127
Chemnitz, Germany, 09113
Dresden, Germany, 01307
Düsseldorf, Germany, 40225
Erfurt, Germany, 99089
Erlangen, Germany, 91054
Frankfurt am Main, Germany, 60528
Freiburg, Germany, 79106
Göttingen, Germany, 37075
Idar-Oberstein, Germany, 55743
Kiel, Germany, 24105
Köln, Germany, 50937
Leipzig, Germany, 04103
Mannheim, Germany, 68167
Marburg, Germany, 35043
Muenchen, Germany, 81377
München, Germany, 81675
Münster, Germany, 48149
Regensburg, Germany, 93053
Tübingen, Germany, 72076
Ulm, Germany, 89081
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00967330     History of Changes
Other Study ID Numbers: ML21965  2009-010390-21 
Study First Received: June 16, 2009
Results First Received: October 20, 2015
Last Updated: October 20, 2015
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Irinotecan
Temozolomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 28, 2016