- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01474239
A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma
February 16, 2016 updated by: Hoffmann-La Roche
Randomized Non Comparative Phase II Trial With Bevacizumab and Fotemustine in the Treatment of Recurrent Glioblastoma
This randomized, non-comparative study will evaluate the efficacy and safety of Avastin (bevacizumab) in patients with recurrent glioblastoma.
Patients will be randomized to receive Avastin 10 mg/kg intravenously every 2 weeks or fotemustine 75 mg/m2 on days 1, 8 and 15, followed by, after a 5 weeks interval, 100 mg/m2 intravenously every 3 weeks.
Treatment with fotemustine serves as a calibration arm and no formal efficacy comparison will be made between the two treatment arms.
The anticipated time of study treatment is until disease progression or unacceptable toxicity.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
91
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Campania
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Napoli, Campania, Italy, 80131
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Emilia-Romagna
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Bologna, Emilia-Romagna, Italy, 40133
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Lazio
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Roma, Lazio, Italy, 00168
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Liguria
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Genova, Liguria, Italy, 16128
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Lombardia
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Milano, Lombardia, Italy, 20132
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Milano, Lombardia, Italy, 20133
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Puglia
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San Giovanni Rotondo, Puglia, Italy, 71013
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Umbria
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Terni, Umbria, Italy, 05100
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Veneto
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Padova, Veneto, Italy, 35128
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Treviso, Veneto, Italy, 31100
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Adult patients, >/=18 years of age
- Diagnosis of recurrent glioblastoma multiforme (Grade IV)
- Previous treatment with temozolomide and radiotherapy
- First recurrence after standard adjuvant treatment (surgery, followed by radiotherapy and chemotherapy)
- Adequate hematological, biochemical and organ functions
Exclusion Criteria:
- Previous treatment with Avastin or other anti-angiogenic drugs
- Residual relevant toxicity resulting from previous therapy
- Radiotherapy within the 3 months prior to the diagnosis of disease progression
- Chemotherapy in the previous 4 weeks
- Other active or inactive malignancies (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma)
- Clinically significant cardiovascular diseases
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Calibration Arm
|
75 mg/m2 intravenously on days 1, 8 and 15 followed by, after a 5 weeks interval, 100 mg/m2 on day 1 of a 3-weeks cycle.
Until disease progression or unacceptable toxicity
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Experimental: Investigational Arm
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10 mg/kg every 2 weeks intravenously until disease progression or unacceptable toxicity
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Alive 6 Months After Start of Treatment
Time Frame: 6 months
|
Overall survival (OS) was defined as the time in months from the start of treatment to death due to any cause.
If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of magnetic resonance imaging (MRI) assessment, date of last treatment, date of discontinuation and date of last available follow-up visit.
Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.
|
6 months
|
Overall Survival (OS)
Time Frame: Baseline until death (up to 691 days)
|
OS was defined as the time in months from the start of treatment to death due to any cause.
If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit.
Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.
|
Baseline until death (up to 691 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Who Were Alive and Progression Free 6 Months After Start of Treatment
Time Frame: 6 months
|
Progression-free survival (PFS) was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first.
PFS was estimated by the Kaplan-Meier method.
Progression was assessed using Response Assessment in Neuro-Oncology (RANO) or Macdonald Response Criteria, whichever occurred first.
As per the RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).
As per the Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration.
|
6 months
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Progression-Free Survival (PFS)
Time Frame: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
|
PFS was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first.
PFS was estimated by the Kaplan-Meier method.
Progression was assessed using the RANO or the Macdonald Response Criteria, whichever occurred first.
As per RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).
As per Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration.
|
Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
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Percentage of Participants Alive 9 Months After Start of Treatment
Time Frame: 9 months
|
OS was defined as the time in months from the start of treatment to death due to any cause.
If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit.
Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.
|
9 months
|
Percentage of Participants Alive 12 Months After Start of Treatment
Time Frame: 12 months
|
OS was defined as the time in months from the start of treatment to death due to any cause.
If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit.
Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.
|
12 months
|
Percentage of Participants Alive 30 Days After Last Dose of Study Drug
Time Frame: 30 days after last dose of study drug (up to Day 600)
|
OS was defined as the time in months from the start of treatment to death due to any cause.
If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit.
Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.
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30 days after last dose of study drug (up to Day 600)
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Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
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Percentage of participants achieving CR or PR as overall response between first drug administration and documented disease progression were calculated.
Tumor response was evaluated according to both the RANO and the Macdonald response criteria.
As per Macdonald criteria, CR was defined as the disappearance of all enhancing disease, sustained for at least 4 weeks, and no new lesions along with clinical features of clinically stable or improved, with no corticosteroid; PR was defined as a 50% or more decrease of all measurable enhancing lesions, sustained for at least 4 weeks, and no new lesion along with clinical features of clinically stable or improved, with stable or reduced corticosteroids.
RANO criteria defined CR and PR the same as Macdonald criteria with the following additions: CR - improved non enhancing T2/FLAIR lesions; PR - no progression of non-measurable disease, stable or improved non enhancing FLAIR/T2 lesions.
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Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
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Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72
Time Frame: Screening, Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72
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EORTC QLQ-C30: included global health status/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties).
Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent').
Scores were averaged and transformed to 0-100 scale; a higher score for Global QOL/functional scales indicates better level of QOL/functioning, or a higher score for symptom scale indicates greater degree of symptoms.
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Screening, Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72
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Percentage of Participants With Corticosteroid Initiation During the Study Period
Time Frame: Baseline until recurrence (up to 691 days)
|
Corticosteroid initiation was assessed in participants not receiving corticosteroids at screening.
The participant had the event if he/she started on corticosteroids with a dosage greater than equal to (>/=) 2 mg dexamethasone equivalent.
|
Baseline until recurrence (up to 691 days)
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Time to Corticosteroid Initiation
Time Frame: Baseline until recurrence (up to 691 days)
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Time to corticosteroid initiation was defined as the time from screening to the start date of the first corticosteroid administration in participants not receiving corticosteroids at screening.
The participant had the event if he/she started on corticosteroids with a dosage ≥2 mg dexamethasone equivalent.
Instead, if the participant was not known to have the event, time was censored at the last available visit date.
Time to corticosteroid initiation was estimated using Kaplan Meier method.
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Baseline until recurrence (up to 691 days)
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Percentage of Participants in Each Class of Corticosteroid Use
Time Frame: Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, post-treatment follow-up (up to Day 691)
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Corticosteroid use was classified as: 1.
No Change (if corticosteroid dose at each assessment was equal to baseline); 2. Decreased (if corticosteroid dose at each assessment was lower than baseline); 3. Increased (corticosteroid dose at each assessment was greater than baseline).
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Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, post-treatment follow-up (up to Day 691)
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Percentage of Participants With Karnofsky Performance Status (KPS) Deterioration
Time Frame: Baseline until KPS deterioration (up to 691 days)
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Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening.
KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
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Baseline until KPS deterioration (up to 691 days)
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Time to Karnofsky Performance Status (KPS) Deterioration
Time Frame: Baseline until KPS deterioration (up to 691 days)
|
Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score.
Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening.
KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
Time to KPS deterioration was estimated using Kaplan Meier method.
If the participant was not known to have the event, time was censored at the last available visit date.
|
Baseline until KPS deterioration (up to 691 days)
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Percentage of Participants With World Health Organization (WHO) Performance Status (PS) Deterioration
Time Frame: Baseline until WHO PS deterioration (Up to 691 days)
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WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value.
WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks.
|
Baseline until WHO PS deterioration (Up to 691 days)
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Time to WHO PS Deterioration
Time Frame: Baseline until WHO PS deterioration (Up to 691 days)
|
Time to WHO PS deterioration was defined as the time from randomization to the first date of deterioration of the WHO performance status score.
WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value.
WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks.
|
Baseline until WHO PS deterioration (Up to 691 days)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2011
Primary Completion (Actual)
December 1, 2013
Study Completion (Actual)
December 1, 2013
Study Registration Dates
First Submitted
November 8, 2011
First Submitted That Met QC Criteria
November 15, 2011
First Posted (Estimate)
November 18, 2011
Study Record Updates
Last Update Posted (Estimate)
March 15, 2016
Last Update Submitted That Met QC Criteria
February 16, 2016
Last Verified
September 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
- Fotemustine
Other Study ID Numbers
- ML25739
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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