Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Fotemustine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

10 mg/kg every 2 weeks intravenously until disease progression or unacceptable toxicity

bevacizumab [Avastin]

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

fotemustine

Clinical Trials

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.

A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma

Randomized Non Comparative Phase II Trial With Bevacizumab and Fotemustine in the Treatment of Recurrent Glioblastoma

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.

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.

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.

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.

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.

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.

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.

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.

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).

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 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.

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.

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.

Hoffmann-La Roche

Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.

Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.

Total

Age, Continuous

Sex: Female, Male

Safety population included all randomized participants with at least one administration of the study drug and at least one safety assessment.

Medical Communications

The 6-month OS rate (OS-6) for bevacizumab was compared to the expected proportion of 0.60 under null hypothesis (ineffective treatment) with the application of the exact binomial test. The one-tailed statistical hypotheses was p0 less than or equal to (≤) 0.60 (null hypothesis) versus pA greater than or equal to (≥) 0.77 (alternative hypothesis), where p is the estimated probability of survival at 6 months.

Intent-to-Treat (ITT) population included all randomized participants with at least one administration of the study drug.

Percentage of Participants Alive 6 Months After Start of Treatment

Overall Survival (OS)

Percentage of Participants Who Were Alive and Progression Free 6 Months After Start of Treatment

Progression-Free Survival (PFS)

Percentage of Participants Alive 9 Months After Start of Treatment

ITT population. Here, the number of participants analyzed signified participants with evaluable data for this outcome.

Percentage of Participants Alive 12 Months After Start of Treatment

Percentage of Participants Alive 30 Days After Last Dose of Study Drug

RANO Evaluation

MacDonald Evaluation

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)

Physical Functioning (Fn): Screening (n=58,31)

Physical Fn: Change at Week 8 (n=27,16)

Physical Fn: Change at Week 16 (n=15,7)

Physical Fn: Change at Week 24 (n=14,1)

Physical Fn: Change at Week 32 (n=7,2)

Physical Fn: Change at Week 40 (n=9,1)

Physical Fn: Change at Week 48 (n=4,1)

Physical Fn: Change at Week 56 (n=4,0)

Physical Fn: Change at Week 64 (n=1,0)

Physical Fn: Change at Week 72 (n=1,0)

Role Fn: Screening (n=58,31)

Role Fn: Change at Week 8 (n=27,16)

Role Fn: Change at Week 16 (n=15,7)

Role Fn: Change at Week 24 (n=14,1)

Role Fn: Change at Week 32 (n=7,2)

Role Fn: Change at Week 40 (n=9,1)

Role Fn: Change at Week 48 (n=4,1)

Role Fn: Change at Week 56 (n=4,0)

Role Fn: Change at Week 64 (n=1,0)

Role Fn: Change at Week 72 (n=1,0)

Emotional Fn: Screening (n=58,31)

Emotional Fn: Change at Week 8 (n=27,16)

Emotional Fn: Change at Week 16 (n=15,7)

Emotional Fn: Change at Week 24 (n=14,1)

Emotional Fn: Change at Week 32 (n=7,2)

Emotional Fn: Change at Week 40 (n=9,1)

Emotional Fn: Change at Week 48 (n=4,1)

Emotional Fn: Change at Week 56 (n=4,0)

Emotional Fn: Change at Week 64 (n=1,0)

Emotional Fn: Change at Week 72 (n=1,0)

Cognitive Fn: Screening (n=58,31)

Cognitive Fn: Change at Week 8 (n=27,16)

Cognitive Fn: Change at Week 16 (n=15,7)

Cognitive Fn: Change at Week 24 (n=14,1)

Cognitive Fn: Change at Week 32 (n=7,2)

Cognitive Fn: Change at Week 40 (n=9,1)

Cognitive Fn: Change at Week 48 (n=4,1)

Cognitive Fn: Change at Week 56 (n=4,0)

Cognitive Fn: Change at Week 64 (n=1,0)

Cognitive Fn: Change at Week 72 (n=1,0)

Social Fn: Screening (n=58,31)

Social Fn: Change at Week 8 (n=27,16)

Social Fn: Change at Week 16 (n=15,7)

Social Fn: Change at Week 24 (n=14,1)

Social Fn: Change at Week 32 (n=7,2)

Social Fn: Change at Week 40 (n=9,1)

Social Fn: Change at Week 48 (n=4,1)

Social Fn: Change at Week 56 (n=4,0)

Social Fn: Change at Week 64 (n=1,0)

Social Fn: Change at Week 72 (n=1,0)

QOL: Screening (n=58,31)

QOL: Change at Week 8 (n=27,16)

QOL: Change at Week 16 (n=15,7)

QOL: Change at Week 24 (n=14,1)

QOL: Change at Week 32 (n=7,2)

QOL: Change at Week 40 (n=9,1)

QOL: Change at Week 48 (n=4,1)

QOL: Change at Week 56 (n=4,0)

QOL: Change at Week 64 (n=1,0)

QOL: Change at Week 72 (n=1,0)

Fatigue: Screening (n=58,31)

Fatigue: Change at Week 8 (n=27,16)

Fatigue: Change at Week 16 (n=15,7)

Fatigue: Change at Week 24 (n=14,1)

Fatigue: Change at Week 32 (n=7,2)

Fatigue: Change at Week 40 (n=9,1)

Fatigue: Change at Week 48 (n=4,1)

Fatigue: Change at Week 56 (n=4,0)

Fatigue: Change at Week 64 (n=1,0)

Fatigue: Change at Week 72 (n=1,0)

Nausea: Screening (n=58,31)

Nausea: Change at Week 8 (n=27,16)

Nausea: Change at Week 16 (n=15,7)

Nausea: Change at Week 24 (n=14,1)

Nausea: Change at Week 32 (n=7,2)

Nausea: Change at Week 40 (n=9,1)

Nausea: Change at Week 48 (n=4,1)

Nausea: Change at Week 56 (n=4,0)

Nausea: Change at Week 64 (n=1,0)

Nausea: Change at Week 72 (n=1,0)

Pain: Screening (n=58,31)

Pain: Change at Week 8 (n=27,16)

Pain: Change at Week 16 (n=15,7)

Pain: Change at Week 24 (n=14,1)

Pain: Change at Week 32 (n=7,2)

Pain: Change at Week 40 (n=9,1)

Pain: Change at Week 48 (n=4,1)

Pain: Change at Week 56 (n=4,0)

Pain: Change at Week 64 (n=1,0)

Pain: Change at Week 72 (n=1,0)

Dyspnea: Screening (n=58,31)

Dyspnea: Change at Week 8 (n=27,16)

Dyspnea: Change at Week 16 (n=15,7)

Dyspnea: Change at Week 24 (n=14,1)

Dyspnea: Change at Week 32 (n=7,2)

Dyspnea: Change at Week 40 (n=9,1)

Dyspnea: Change at Week 48 (n=4,1)

Dyspnea: Change at Week 56 (n=4,0)

Dyspnea: Change at Week 64 (n=1,0)

Dyspnea: Change at Week 72 (n=1,0)

ITT population. Here, the number of participants analyzed signified participants with evaluable data for this outcome, and "n" signified participants with evaluable data for specified category for each arm, respectively.

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

ITT population. Number of participants analyzed signified participants who were not receiving corticosteroids at screening.

Percentage of Participants With Corticosteroid Initiation During the Study Period

Spots Global Cancer Trial Database for A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial