A Comparison of Continuous Bevacizumab (Avastin) Treatment or Placebo in Addition to Lomustine Followed by Standard of Care After Disease Progression in Participants With Glioblastoma

Summary

This multicenter, double-blind, placebo-controlled, randomized study will evaluate the efficacy and safety of the addition of bevacizumab treatment to lomustine (in 2nd-line \[2L\] treatment) and SOC (in 3rd-line \[3L\] and subsequent lines of treatment) following first-line disease progression (PD1) in participants with newly diagnosed glioblastoma. All enrolled participants will receive 1L treatment with radiotherapy, temozolomide, and bevacizumab. At PD1, eligible participants will be randomized (1:1) to receive 2L treatment with either bevacizumab plus lomustine or placebo plus lomustine. After second-line disease progression (PD2), participants will receive 3L treatment and will continue blinded bevacizumab or placebo with the addition of an SOC agent. Following third-line disease progression (PD3), participants will receive subsequent lines of treatment and will either continue blinded bevacizumab or placebo (at the discretion of the investigator), or switch to open-label bevacizumab (at the choice of the participant).

Conditions

• Glioblastoma

Interventions

DRUG

Bevacizumab

Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks (Q2W) throughout the study, with the exception of bevacizumab monotherapy prior to PD1, which will be given as 15 mg/kg IV every 3 weeks (Q3W).

DRUG

Lomustine

Lomustine will be administered at a dose of 90 milligrams per square meter (mg/m\^2) orally (PO) every 6 weeks (Q6W), with a cap of 160 milligrams (mg) per dose. In the absence of hematologic toxicity following the first dose, the second and subsequent doses may be increased to 110 mg/m\^2 PO Q6W, with a cap of 200 mg per dose.

DRUG

Placebo

Placebo will be administered via IV infusion, in a formulation matched to bevacizumab, Q2W after randomization.

RADIATION

Radiotherapy

Radiotherapy will be administered for a total dose of 60 Gray (Gy), administered in 2-Gy fractions, 5 days per week for 6 weeks during first-line treatment.

DRUG

Temozolomide

Temozolomide will be administered orally (PO) as 75 mg/m\^2 per day for the first 6 weeks of first-line treatment (concurrent treatment), followed by 6 cycles (28 days each) as follows: 150 mg/m\^2 per day for the first 5 days of Cycle 1, then 200 mg/m\^2 per day (if permitted by the participant's hematological and non-hematological toxicity profile) for the first 5 days of Cycles 2-6.

DRUG

SOC Agent

The choice of SOC agent will be at the discretion of investigator. The SOC agent will be administered during third-line treatment and subsequent lines, as per standard practice.

Sponsors & Collaborators

• Hoffmann-La Roche

  lead INDUSTRY

Principal Investigators

• Clinical Trials · Hoffmann-La Roche

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-08-19

Primary Completion

2017-01-13

Completion

2017-05-05

Countries

• Austria
• Bulgaria
• Canada
• Croatia
• Estonia
• France
• Greece
• Italy
• Latvia
• Portugal
• Romania
• Spain
• Sweden
• Turkey (Türkiye)
• United Kingdom

Study Locations