A Study of Avastin® (Bevacizumab) in Combination With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00943826
First received: July 17, 2009
Last updated: September 6, 2013
Last verified: September 2013

July 17, 2009
September 6, 2013
June 2009
March 2012   (final data collection date for primary outcome measure)
  • Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator [ Time Frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)] ] [ Designated as safety issue: No ]

    PFS was defined as the time from randomization to disease progression or death due to any cause.

    Disease progression (PD) was assessed by the investigator using adapted Macdonald response criteria (modified World Health Organization (WHO) criteria) based on 3 components: radiological tumor assessments using Magnetic Resonance Imaging (MRI) scans, neurological assessment and changes in corticosteroid use.

    PD was determined as ≥ 25% increase in the sum of the products of the perpendicular longest diameters of all index lesions (enhancing, measurable) compared with the smallest recorded sum (nadir) during the study or unequivocal progression of existing non-index lesions (non-enhancing and enhancing, non-measurable) or unequivocal appearance of new lesions); or neurological worsening (if corticosteroid dose is stable or increased) with no need for a confirmatory scan.

    Data from the final analysis is presented.

  • Co-Primary: Overall Survival (OS) [ Time Frame: Randomization until Overall Survival Event ] [ Designated as safety issue: No ]
    Overall Survival was defined as the time from randomization to death due to any cause.
  • Progression-free survival [ Time Frame: Assessments in weeks 10,18, 26 and 34 and at 9-weekly intervals thereafter ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Assessments in weeks 10,18, 26 and 34 and at 9-weekly intervals thereafter ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00943826 on ClinicalTrials.gov Archive Site
  • Progression-free Survival (PFS) as Assessed by an Independent Review Facility [ Time Frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)] ] [ Designated as safety issue: No ]
    An Independent Review Facility reviewed the magnetic resonance imaging (MRI) scans used by the investigator to evaluate radiological tumor response. PFS was defined as the time from randomization to disease progression or death due to any cause.
  • Percentage of Participants With One-Year Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of participants who are still alive 1 year post randomization.
  • Percentage of Participants With Two-year Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Percentage of participants who are still alive 2 years post randomization.
  • Duration of Stable/Improved Health Related Quality of Life (HRQoL) Using the European Organisation for Research and Treatment of Cancer Scales (EORTC) QLQ-C30 and BN20 [ Time Frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)] ] [ Designated as safety issue: No ]
    Stable and Improved HRQoL during PFS time was determined using the EORTC QLQ-C30 and BN20 questionnaires. The EORTC QLQ-C30 is a 30-item self-reported questionnaire in 5 functional scales (physical,role,emotional,cognitive,social), 3 symptoms scales, 6 single-item measures and a global health status/QoL scale.Patients rated the items on a 4-point scale: 1=not at all to 4=very much.Global health status/QoL items were rated on a 7-point scale: 1=very poor to 7=excellent. The BN20 consisted of 20 questions in 4 scales(future uncertainty,visual disorder,motor dysfunction,communication deficit) and 7 single-item measures rated on a 4-point scale: 1=not at all to 4=very much. A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100. Stable HRQoL was defined as a change from baseline within 10 points.Improved HRQoL is defined as an increase of at least 10 points for functioning/global health status and a decrease of at least 10 points for symptoms.
  • Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: Until data cutoff= 31 March 2012 (up to 34 months) ] [ Designated as safety issue: No ]

    An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

    A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  • Survival rates [ Time Frame: 1 year and 2 years ] [ Designated as safety issue: No ]
  • Health-related quality of life [ Time Frame: assessments in weeks 10, 18, 26 and 34 and at 9-weekly intervals thereafter ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Avastin® (Bevacizumab) in Combination With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Glioblastoma
Not Provided

This 2 arm study investigated the efficacy and safety of the addition of bevacizumab (Avastin®) to the current standard of care (multimodality therapy of concurrent radiotherapy plus temozolomide followed by adjuvant temozolomide) as compared to the current standard of care alone. Patients were randomly assigned to either the Avastin® (10 mg/kg iv q2w) or the placebo arm, in combination with radiation therapy (total dose 60 Gy, administered as 2 Gy fractions, 5 days/week)plus temozolomide (75 mg/m2 po daily) for 6 weeks. After a 4 week treatment break, patients continued to receive Avastin® (10 mg/kg iv q2w) or placebo, plus temozolomide (150-200 mg/m2 po daily on days 1-5 of each 4 week cycle) for 6 cycles of maintenance treatment. Following the maintenance phase, Avastin® (15 mg/kg iv q3w) or placebo monotherapy was continued. The anticipated time on study treatment was until disease progression/unacceptable toxicity.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Glioblastoma
  • Drug: bevacizumab [Avastin®]
    10 mg/kg intravenously every 2 weeks in the Concurrent and Maintenance Phases. 15 mg/kg intravenously every 3 weeks in the Monotherapy Phase.
  • Drug: Placebo
    Intravenously every 2 weeks in the Concurrent and Maintenance Phases and every 3 weeks in the Monotherapy Phase.
  • Drug: temozolomide
    75 mg/m2 once daily for 6 weeks, followed by 150-200 mg/m2 once daily on days 1-5 of each 6 x 4 week cycle.
  • Radiation: Radiation therapy
    30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks
  • Experimental: Bevacizumab + RT+Temozolomide
    In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gy given 5 days per week for 6 week and temozolomide 75 mg/m^2 daily for a maximum of 49 days and bevacizumab 10 mg/kg intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity.
    Interventions:
    • Drug: bevacizumab [Avastin®]
    • Drug: temozolomide
    • Radiation: Radiation therapy
  • Placebo Comparator: Placebo + RT+ Temozolomide
    In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 week and temozolomide 75 mg/m^2 daily for a maximum of 49 days and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity.
    Interventions:
    • Drug: Placebo
    • Drug: temozolomide
    • Radiation: Radiation therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
921
April 2014
March 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • newly diagnosed glioblastoma;
  • World Health Organization (WHO) performance status <=2;
  • stable or decreasing corticosteroid dose within 5 days prior to randomization.

Exclusion Criteria:

  • evidence of recent hemorrhage or postoperative magnetic resonance imaging (MRI) of brain;
  • any prior chemotherapy or immunotherapy for glioblastomas and low grade astrocytomas;
  • any prior radiotherapy to brain;
  • clinically significant cardiovascular disease;
  • history of >=grade 2 hemoptysis within 1 month prior to randomization;
  • previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status for enrollment into a clinical trial.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Canada,   Denmark,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Portugal,   Romania,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom
 
NCT00943826
BO21990, 2008-006146-26
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP