Bevacizumab in Recurrent Grade II and III Glioma

Phase 2

Completed

• Conditions: Central Nervous System Tumors
• Interventions: Drug: Temozolomide; Biological: Bevacizumab

• Registration Number: NCT01164189
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide is more effective when given with or without bevacizumab in treating patients with recurrent glioma.

PURPOSE: This randomized clinical trial is studying how well temozolomide works with or without bevacizumab in treating patients with recurrent glioma.

Detailed Description

OBJECTIVES:

Primary

* To document the activity of both combination temozolomide plus bevacizumab and temozolomide alone in patients with recurrent grade II or grade III glioma without 1p/19q co-deletion.

Secondary

* To characterize the safety of treatment in these patients.

* To document the quality of life and cognitive functioning, as a measure of clinical benefit, of these patients.

* To explore qualification or occurrence of prognostic and/or predictive biomarkers of activity or efficacy in these patients. (exploratory)

* To document the discordances between RANO and Macdonald's criteria for the evaluation of response and progression. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to institution, initial histology (grade II vs grade III), WHO performance status (0-1 vs 2), and prior treatment (radiotherapy \[RT\] alone, temozolomide \[TMZ\] or procarbazine, lomustine and vincristine \[PCV\] alone vs TMZ/RT). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive oral temozolomide as in arm I and bevacizumab IV over 90 minutes on days 1 and 15. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the Controlled Oral Word Association test, and the Trail Making tests A and B). Quality-of-life assessment questionnaires, including EORTC QLQ-C30 and EORTC-BN20, are completed by both patients and caregivers/relatives at baseline and then periodically.

Frozen tumor biopsies or paraffin blocks and blood specimens are collected for bio-banking and translational research.

After completion of study therapy, patients are followed up every 3 months.

Study Timeline

• Study First Submitted: 2010-07-15
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Study Start: 2011-02
• Primary Completion: 2017-01-19
• Study Completion: 2017-09-24
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-27
• Last Update Posted: 2019-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Temozolomide	Temozolomide	Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles
Temozolomide + Bevacizumab	Bevacizumab	TMZ: Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles Beva: 10 mg/kg bw IV in 90 minutes on day 1 and 14, 4 week cycles.
Temozolomide + Bevacizumab	Temozolomide	TMZ: Administered orally on day 1-5, 150-200 mg/m(2), repeated every 4 weeks, up to 12 cycles Beva: 10 mg/kg bw IV in 90 minutes on day 1 and 14, 4 week cycles.

Primary Outcome Measures

Name	Time	Method
Probability of survival at 1 year	From the date of randomization up to the date of death, assessed up to 12 months	Patients alive at 12 months

Secondary Outcome Measures

Name	Time	Method
Objective response rate and duration of response	From the date of randomization until disease progression	Objective response includes best overall responses complete response and partial response
Progression-free survival	From the date of randomization until the date of objective progression or the date of patient's death whichever occurs first
Overall survival and survival at 24 months	From the date of randomization up to the date of death
Safety	After the first ten patients in each arm have completed the first two cycles or have stopped treatment, an interim safety review of those patients will be conducted.
Clinical/neurological deterioration-free survival	From the date of randomization until the date of neurological deterioration
Steroid use	At baseline and every 3 months untill lost to follow-up
Quality of life of patients and caregivers/relatives	At baseline and every 3 months untill lost to follow-up
Cognitive deterioration	At baseline and every 3 months untill lost to follow-up

Trial Locations

Locations (39)

Landesnervenklinik Wagner Jauregg; 🇦🇹 Linz, Austria

Medical University Vienna - General Hospital AKH; 🇦🇹 Vienna, Austria

Universitair Ziekenhuis Brussel; 🇧🇪 Brussel, Belgium

U.Z. Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

CHRU de Lille; 🇫🇷 Lille, France

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer; 🇫🇷 Lyon, France

Assistance Publique - Hôpitaux de Marseille - Hôpital de La Timone; 🇫🇷 Marseille, France

CHU de Nice - Hopital Pasteur; 🇫🇷 Nice, France

CHU Pitie-Salpetriere; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Paris, France

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