Neoplasms

All Conditions

Rare Diseases

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

Irinotecan

Temozolomide

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

bevacizumab [Avastin]

irinotecan

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

temozolomide

Clinical Trials

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.

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

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.

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 was defined as the time from randomization to death from any cause. OS was estimated using Kaplan-Meier method.

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.

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.

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.

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.

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.

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.

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.

Participants used corticosteroids for the glioblastoma condition. Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.

Hoffmann-La Roche

In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.

Bevacizumab + Irinotecan

In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator or and, if eligible.

In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.

Total

Age, Continuous

Sex: Female, Male

The randomized (RND) population was defined to include all participants randomized.

Data for time to treatment failure were not collected as this outcome was removed as per changes in planned analysis.

Medical Communications

Intent-to-treat (ITT) population included participants randomized for whom it cannot be ruled out, that they took study medication at least once and where primary variable was measured at least once under study medication. Data were analyzed according to the treatment randomized (as randomized).

Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months

ITT population. Data were analyzed according to the treatment randomized (as randomized).

Progression-Free Survival (PFS)

Overall Survival (OS)

Persisting non-hematological toxicity CTCAE Grade3

CNS hemorrhagic event (CTCAE Grade >1)

Gastro-intestinal perforation (CTCAE Grade 1-4)

Other

Participant's wish

Progressive disease

Proteinuria (nephrotic syndrome) (CTCAE Grade 4)

Regular

Repeated CTCAE Grade 4 hematological toxicity

Venous thrombosis/embolism

Wound dehiscence requiring medical intervention

Wound dehiscence requiring surgical intervention

Percentage of Participants Who Discontinued

Response rate based on participants with CR at 4 weeks after RT.

The response rate based on participants with CR at \>4 weeks after RT.

The response rate based on participants with CR at Month 6.

Response rate based on participants with CR or PR at 4 weeks after RT.

Response rate based on participants with CR and PR at \>4 weeks after RT.

Response rate based on participants with CR or PR at Month 6.

CR at 4 weeks after RT (n=110,46)

CR at >4 weeks after RT (n=95,35)

CR at Month 6 (n=91,28)

CR or PR at 4 Week after RT (n=110,46)

CR or PR at >4 Week after RT (n=95,35)

CR or PR at Month 6 (n=91,28)

ITT population. Data were analyzed according to the treatment randomized (as randomized). Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable of specified time-point.

Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)

Screening: Initial Flair Lesion (n=116,54)

Screening:Stable Flair Lesion (n=116,54)

Baseline:Decreased FLAIR Lesions (n=105,46)

Baseline:Initial FLAIR Lesions (n=105,46)

Baseline:Progressive FLAIR Lesions (n=105,46)

Baseline: Stable FLAIR Lesions (n=105,46)

Month 6:Progressive FLAIR Lesions (n=91,28)

Month 6: Stable FLAIR Lesions (n=91,28)

Therapy Dis.:Decreased FLAIR Lesions (n=55,31)

Therapy Dis.:Progressiv FLAIR Lesions (n=55,31)

Therapy Dis.:Stable FLAIR Lesions (n=55,31)

ITT population. Here, n = participants with at least 1 assessment during specified time-point.

Percentage of Participants With Response on FLAIR Imaging

Physical Functioning. Analysis of variance (ANOVA) included all post-baseline data (Months 3 through 21).

Role Functioning. ANOVA included all post-baseline data (Months 3 through 21).

Emotional Functioning. ANOVA included all post-baseline data (Months 3 through 21).

Cognitive Functioning. ANOVA included all post-baseline data (Months 3 through 21).

Social Functioning. ANOVA included all post-baseline data (Months 3 through 21).

Global Health Status /QoL. ANOVA included all post-baseline data (Months 3 through 21).

Fatigue. ANOVA included all post-baseline data (Months 3 through 21).

Nausea/Vomiting. ANOVA included all post-baseline data (Months 3 through 21).

Pain. ANOVA included all post-baseline data (Months 3 through 21).

Dyspnoea. ANOVA included all post-baseline data (Months 3 through 21).

Insomnia. ANOVA included all post-baseline data (Months 3 through 21).

Appetite loss. ANOVA included all post-baseline data (Months 3 through 21).

Constipation. ANOVA included all post-baseline data (Months 3 through 21).

Diarrhoea. ANOVA included all post-baseline data (Months 3 through 21).

Financial Problems. ANOVA included all post-baseline data (Months 3 through 21).

Physical Functioning

Role Functioning

Emotional Functioning

Cognitive Functioning

Social Functioning

Global health Status /QoL (ql)

Fatique

Nausea/Vomitting

Pain

Dyspnoea

Insomnia

Appetite loss

Constipation

Diarrhoea

Financial Problems

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)

Future uncertainty. ANOVA included all post-baseline data (Months 3 through 21).

Visual disorder. ANOVA included all post-baseline data (Months 3 through 21).

Motor dysfunction. ANOVA included all post-baseline data (Months 3 through 21).

Communication deficit. ANOVA included all post-baseline data (Months 3 through 21).

Headaches. ANOVA included all post-baseline data (Months 3 through 21).

Seizures. ANOVA included all post-baseline data (Months 3 through 21).

Drowsiness. ANOVA included all post-baseline data (Months 3 through 21).

Hair loss. ANOVA included all post-baseline data (Months 3 through 21).

Itchy skin. ANOVA included all post-baseline data (Months 3 through 21).

Weakness of legs. ANOVA included all post-baseline data (Months 3 through 21).

Bladder control. ANOVA included all post-baseline data (Months 3 through 21).

Future uncertainty

Visual disorder

Motor dysfunction

Communication deficit

Headaches

Drowsines

Hair loss

Itchy skin

Weakness of legs

Bladder control

Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)

Orientation to time and place. ANOVA included all post-baseline data (Months 3 through 21).

Immediate recall. ANOVA included all post-baseline data (Months 3 through 21).

Repetitions required. ANOVA included all post-baseline data (Months 3 through 21).

Calculations. ANOVA included all post-baseline data (Months 3 through 21).

Short-term verbal memory. ANOVA included all post-baseline data (Months 3 through 21).

Language and construct ability. ANOVA included all post-baseline data (Months 3 through 21).

Total score. ANOVA included all post-baseline data (Months 3 through 21).

Orientation to time and place

Immediate recall

Repetitions required

Calculations

Short-term verbal memory

Language and construct ability

Total Score

Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)

KPS score. ANOVA included all post-baseline data (Months 3 through 21).

Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)

The safety population (SAF) was defined to include all participants who received at least 1 dose of study medication. Data were analyzed according to the treatment actually received (as treated).

Percentage of Participants Who Received Corticosteroid for Glioblastoma

Data for this outcome measure were not collected as this outcome was removed as per changes in planned analysis.

Spots Global Cancer Trial Database for A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial