NCT01860638|CompletedPhase 2

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

A Double-Blind, Placebo-Controlled, Randomised, Phase II Study Evaluating the Efficacy and Safety of Addition of Continuous Multiple Line Bevacizumab Treatment to Lomustine in Second (2nd)-Line Followed by Standard of Care (SOC) in Third (3rd)-Line and Beyond Compared to Addition of Placebo, Following First Progression of Disease (PD1) in Patients With Glioblastoma (GBM) After First (1st)-Line Treatment With Radiotherapy, Temozolomide and Bevacizumab

Hoffmann-La Roche ClinicalTrials.gov

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2 other identifiers

MO283472012-003138-17

Study Type

interventional

Target

296

Locations

14 countries

Sites

Timeline

RegisteredMay 2013

StartedAug 2013

CompletionMay 2017

Brief 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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

296

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Aug 2013

Typical duration for phase_2

Geographic Reach

14 countries

49 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.7 years study duration

First Submitted

Initial submission to the registry

May 21, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

May 23, 2013

Completed

3 months until next milestone

Study Start

First participant enrolled

August 19, 2013

Completed

3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 13, 2017

Completed

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 5, 2017

Completed

Last Updated

April 30, 2018

Status Verified

April 1, 2018

Enrollment Period

3.4 years

First QC Date

May 21, 2013

Last Update Submit

April 26, 2018

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS)
From randomization at PD1 until death from any cause or end of study (overall approximately 35 months)

Secondary Outcomes (25)

Percentage of Participants Alive at 6, 12, and 18 Months from Randomization
At 6, 12, and 18 months after randomization/PD1 (overall up to approximately 35 months)
Progression-Free Survival (PFS) on 2L Treatment According to Modified Response Assessment in Neuro-Oncology (RANO) Criteria
From first administration of randomized treatment until PD2 or death from any cause (overall approximately 18 months)
PFS on 3L Treatment According to Modified RANO Criteria
From first administration of randomized treatment until PD3 or death from any cause (overall approximately 35 months)
Restricted PFS on 3L Treatment According to Modified RANO Criteria
From first administration of treatment after PD2 until PD3 or death from any cause (overall approximately 26 months)
Percentage of Participants with 2L Objective Response of Complete Response (CR) or Partial Response (PR) According to Modified RANO Criteria
From randomization/PD1 until PD2, death, subsequent anticancer therapy, operation/re-operation for glioblastoma, or 13 weeks after last administration of 2L-treatment, whichever occurs first (approximately 18 months overall)
+20 more secondary outcomes

Study Arms (2)

First-Line Bevacizumab followed by Bevacizumab + Lomustine/SOC

EXPERIMENTAL

Participants will receive first-line treatment with radiotherapy, temozolomide, and bevacizumab. All three treatments will be given concurrently for the first 6 weeks, followed by 6 cycles (28 days each) of temozolomide plus bevacizumab, followed by bevacizumab monotherapy until PD1 or unacceptable toxicity. At PD1, participants randomized to bevacizumab will receive bevacizumab plus lomustine until PD2. Following PD2, participants will continue with blinded bevacizumab with the addition of appropriate SOC. Following PD3, for subsequent treatment lines blinded bevacizumab may continue or open-label bevacizumab may be given at the discretion of the investigator and the participant.

Drug: BevacizumabDrug: LomustineRadiation: RadiotherapyDrug: TemozolomideDrug: SOC Agent

First-Line Bevacizumab followed by Placebo + Lomustine/SOC

PLACEBO COMPARATOR

Participants will receive first-line treatment with radiotherapy, temozolomide, and bevacizumab. All three treatments will be given concurrently for the first 6 weeks, followed by 6 cycles (28 days each) of temozolomide plus bevacizumab, followed by bevacizumab monotherapy until PD1 or unacceptable toxicity. At PD1, participants randomized to placebo will receive placebo plus lomustine until PD2. Following PD2, participants will continue with blinded placebo with the addition of appropriate SOC. Following PD3, for subsequent treatment lines blinded bevacizumab may continue or open-label bevacizumab may be given at the discretion of the investigator and the participant.

Drug: BevacizumabDrug: LomustineDrug: PlaceboRadiation: RadiotherapyDrug: TemozolomideDrug: SOC Agent

Interventions

BevacizumabDRUG

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).

Also known as: Avastin