Back to resultsA Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme
Primary Purpose
Glioblastoma Multiforme
Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
bevacizumab [Avastin]
temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 years
- Histological diagnosis of glioblastoma multiforme (GBM) documented by surgical resection or biopsy.
- They should be patients in a first relapse treated with radiotherapy and chemotherapy and chemotherapy based on temozolomide 150-200 mg/m2 on days 1 to 5 every 28 days (Stupp regimen) for at least three cycles. At least 4 weeks must have lapsed since previous chemotherapy and 3 months since the last dose of radiotherapy.
- Use of an effective contraceptive method by patients and their partners.
- Stable or decreasing corticosteroid dose for the five days prior to study entry
- Adequate hematological function
- Adequate liver function
- Adequate kidney function
Exclusion Criteria:
- Signs of recent bleeding at the MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving bleeding changes related to surgery, and presence of punctate hemorrhage in the tumor will be allowed to participate in the study.
- Prior treatment with bevacizumab
- Poorly controlled arterial hypertension
- History of hypertensive crises or hypertensive encephalopathy
- New York Health Association (NYHA) Class II or higher congestive heart failure
- History of myocardial infarction or unstable angina pectoris within six months of study entry
- History of stroke or TIA within six months of study entry
- Significant vascular disease within six months of study entry
- History of hemoptysis > grade 2 according to the NCI CTC criteria within one month of study entry
- Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgery, open biopsy, intracranial biopsy, ventriculoperitoneal shunt, or major traumatic lesion within 28 days of study entry.
- Core needle biopsy (excluding intracranial biopsy) or other minor surgery within seven days of randomization. Placement of a central vascular access device (CVAD) if performed in the two days prior to bevacizumab administration
- History of abdominal fistula or gastrointestinal perforation within six months of study entry
- History of intracranial abscess within six months of randomization
- Any prior malignant neoplasm treated with curative intent in the five years prior to study entry, except for adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
- Patients with any other metabolic or psychological disease
- Hypersensitivity to products derived from Chinese hamster ovary cells or to other humanized or recombinant human antibodies
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A
Arm Description
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) - Percentage of Participants With an Event
PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment.
PFS - Time to Event
PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment. PFS was estimated using the Kaplan-Meier method.
PFS: Probability of Remaining Progression Free at 24 Weeks After Beginning the Study
Secondary Outcome Measures
Overall Survival - Percentage of Participants With an Event
Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact.
Overall Survival - Time to Event
Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact. Median overall survival was estimated using the Kaplan-Meier method.
Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)
Overall response was defined as the percentage of participants who obtained CR or PR using adapted MacDonald criteria. CR: disappearance of all index and non-index lesions, confirmed no less than 4 weeks after assessment, no evidence of disease progression; corticosteroid dosage at or below 20 mg hydrocortisone daily; no neurological changes or an improvement as compared to last disease assessment. PR was defined as: Fifty percent or greater decrease in the sum of products of the larger diameter and the larger perpendicular diameter of all index lesions confirmed no less than 4 weeks after assessment, no evidence of disease progression and the absence of progressive, or non-evaluable disease status for non-index legions; unchanged, or decreased corticosteroid dose as compared to the last disease assessment; no neurological changes or an improvement as compared to the neurological examination at last disease assessment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01115491
Brief Title
A Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme
Official Title
A Single Arm Phase II Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This is a Phase II, national, multicenter, open-label, non-comparative study to investigate the efficacy and safety of bevacizumab and temozolomide in patients with recurrent glioblastoma multiforme (GBM) after a first treatment failure. Patients will receive bevacizumab 10 mg/kg intravenously every two weeks until disease progression, consent withdrawal, or unacceptable toxicity. Anticipated time on study treatment is 12-24 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
Bevacizumab 10 mg/kg body weight will be administered intravenously every two weeks
Intervention Type
Drug
Intervention Name(s)
temozolomide
Intervention Description
Daily by the oral route (dose, 150 mg/m2) on days 1 to 7 and 15 to 21 of each cycle
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) - Percentage of Participants With an Event
Description
PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment.
Time Frame
Baseline (BL), every 28 days, until progression, death or end-of-study, an average of 32 weeks
Title
PFS - Time to Event
Description
PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment. PFS was estimated using the Kaplan-Meier method.
Time Frame
BL, every 28 days, until progression, death or end-of-study, an average of 32 weeks
Title
PFS: Probability of Remaining Progression Free at 24 Weeks After Beginning the Study
Time Frame
BL, 24 weeks (after 6th cycle)
Secondary Outcome Measure Information:
Title
Overall Survival - Percentage of Participants With an Event
Description
Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact.
Time Frame
BL, every 28 days, until death or end-of-study, an average of 32 weeks
Title
Overall Survival - Time to Event
Description
Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact. Median overall survival was estimated using the Kaplan-Meier method.
Time Frame
BL, every 28 days, until death or end-of-study, an average of 32 weeks
Title
Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)
Description
Overall response was defined as the percentage of participants who obtained CR or PR using adapted MacDonald criteria. CR: disappearance of all index and non-index lesions, confirmed no less than 4 weeks after assessment, no evidence of disease progression; corticosteroid dosage at or below 20 mg hydrocortisone daily; no neurological changes or an improvement as compared to last disease assessment. PR was defined as: Fifty percent or greater decrease in the sum of products of the larger diameter and the larger perpendicular diameter of all index lesions confirmed no less than 4 weeks after assessment, no evidence of disease progression and the absence of progressive, or non-evaluable disease status for non-index legions; unchanged, or decreased corticosteroid dose as compared to the last disease assessment; no neurological changes or an improvement as compared to the neurological examination at last disease assessment.
Time Frame
BL, every 28 days, until progression, death or end-of-study, an average of 32 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >= 18 years
Histological diagnosis of glioblastoma multiforme (GBM) documented by surgical resection or biopsy.
They should be patients in a first relapse treated with radiotherapy and chemotherapy and chemotherapy based on temozolomide 150-200 mg/m2 on days 1 to 5 every 28 days (Stupp regimen) for at least three cycles. At least 4 weeks must have lapsed since previous chemotherapy and 3 months since the last dose of radiotherapy.
Use of an effective contraceptive method by patients and their partners.
Stable or decreasing corticosteroid dose for the five days prior to study entry
Adequate hematological function
Adequate liver function
Adequate kidney function
Exclusion Criteria:
Signs of recent bleeding at the MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving bleeding changes related to surgery, and presence of punctate hemorrhage in the tumor will be allowed to participate in the study.
Prior treatment with bevacizumab
Poorly controlled arterial hypertension
History of hypertensive crises or hypertensive encephalopathy
New York Health Association (NYHA) Class II or higher congestive heart failure
History of myocardial infarction or unstable angina pectoris within six months of study entry
History of stroke or TIA within six months of study entry
Significant vascular disease within six months of study entry
History of hemoptysis > grade 2 according to the NCI CTC criteria within one month of study entry
Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
Major surgery, open biopsy, intracranial biopsy, ventriculoperitoneal shunt, or major traumatic lesion within 28 days of study entry.
Core needle biopsy (excluding intracranial biopsy) or other minor surgery within seven days of randomization. Placement of a central vascular access device (CVAD) if performed in the two days prior to bevacizumab administration
History of abdominal fistula or gastrointestinal perforation within six months of study entry
History of intracranial abscess within six months of randomization
Any prior malignant neoplasm treated with curative intent in the five years prior to study entry, except for adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
Patients with any other metabolic or psychological disease
Hypersensitivity to products derived from Chinese hamster ovary cells or to other humanized or recombinant human antibodies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
City
Madrid
ZIP/Postal Code
28040
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Valencia
ZIP/Postal Code
41014
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme
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