A comparison of continuous Avastin treatment or placebo in addition to lomustine followed by standard treatment for worsening brain cancer.

• Register: EUCTR
• Last refreshed on: 9 May 2022
• Main ID: EUCTR2012-003138-17-IE
• Date of registration: 03/05/2013
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A comparison of continuous Avastin treatment or placebo in addition to lomustine followed by standard treatment for worsening brain cancer.
• Scientific title: A double-blind, placebo-controlled, randomized, Phase IIIb 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.
• Date of first enrolment: 17/05/2013
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003138-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Argentina, Austria, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, China, Croatia, Egypt, Estonia, Finland, France, Greece, Ireland, Italy, Latvia, Lithuania, Mexico, Peru, Portugal, Romania, Serbia, Spain, Sweden, Turkey, United Kingdom, Uruguay

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Have provided written informed consent.
• Age = 18 years .
• Karnofsky performance status (KPS) = 60.
• Newly diagnosed, histologically confirmed glioblastoma not previously
treated with chemotherypy or radiotherapy
• If female and not postmenopausal (< 12 months of amenorrhea) or
surgically sterile, must agree to use a highly effective contraceptive
method during the treatment period and for at least 6 months after the
last dose of study drug
• Mandatory tissue collection during pre-study surgery or biopsy for confirmation of the diagnosis and pathology.
• Craniotomy or intracranial biopsy site must be adequately healed.
Study treatment should be initiated > 28 days following the last surgical
procedure.

Principal eligibility criteria at the time of randomisation (following PD1):
• Documented disease progression (PD1)
• Eligibility for 2nd-line treatment with lomustine and bevacizumab as
investigational medicinal products.
• Patients for whom operation or re-operation is indicated before 2ndline starts, tissue submission is mandatory
• Eastern Cooperative Oncology Group (ECOG) performance status is 0-2 when starting 2nd-line treatment
• Bevacizumab was well tolerated and treatment interruption lasted not more than 60 days


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 398
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112

Exclusion criteria:
• Any prior chemotherapy for GBM and low grade astrocytomas.
• Any prior radiotherapy to the brain or prior radiotherapy resulting in a
potential overlap in the radiation field.
• Prior or current anti-angiogenic treatment
•Treatment with any other investigational drug within 28 days or 2
investigational agent half-lives (whichever is longer) prior to first study
treatment
• Inadequate hematological, renal or liver function
• Inadequately controlled hypertension
• Prior history of gastrointestinal perforation or abscess
• Clinically significant cardiovascular disease, NYHA >/= Grade II
congestive heart failure, or serious cardiac arrhythmia uncontrolled by
medication or potentially interfering with protocol treatment
• History or evidence of central nervous system disease unrelated to
cancer unless adequately treated with standard medical therapy
• History or evidence of inherited bleeding diathesis or significant
coagulopathy at risk of bleeding
• Serious non-healing wound, active ulcer, or untreated bone fracture
• Known hypersensitivity to any component of Avastin/placebo or any of
the study drugs
• Active infection requiring intravenous antibiotics at start of study
treatment
• Other malignancy within 5 years prior to study enrollment, except for
carcinoma in situ of the cervix, basal or squamous cell skin cancer,
localized prostate cancer or ductal carcinoma in situ treated with
curative intent
• Pregnant or lactating women
• Participation in any other study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Glioblastoma
MedDRA version: 17.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Avastin
Product Name: Bevacizumab
Product Code: RO4876646/F02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Cenenu
Pharmaceutical Form: Capsule
INN or Proposed INN: Lomustine
CAS Number: 13010-47-4
Current Sponsor code: Ro 021-6173
Other descriptive name: LOMUSTINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: To assess the efficacy of addition of continuous multiple line
bevacizumab treatment to lomustine in 2nd-line followed by standard of care (SOC) in 3rd-line and beyond compared to addition of bevacizumabplacebo, as measured by overall survival (OS) from randomisation at first progression of disease (PD1).

Timepoint(s) of evaluation of this end point: When 250 events have been observed

Primary end point(s): Overall survival (OS)

Secondary Objective: To assess:
• overall survival as measured from randomization at PD1.
• progression free survival from randomization at PD1, to 2nd PD (PD2) (PFS2), and to 3rd PD (PD3) (PFS3).
• response rates (RRs), disease control rates (DCRs), and durations of response at PD2 and PD3.
• the safety of bevacizumab treatment across multiple lines of treatment and from randomization at PD1.
• HRQoL, neurocognitive function (NCF) and resource utilization

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at the time of the primary endpoint (when 250 events have been observed)

Secondary end point(s): - 2nd and 3rd line progression free survival (PFS)
- Response, duration of response and disease control rates in 2nd and 3rd line
- Safety
- Neurocognitive function, Health Related QoL, resource utilization

Secondary ID(s)

NCT01860638

MO28347

2012-003138-17-AT

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 25/03/2013
Contact:

Results

• Results available: Yes
• Date Posted: 12/05/2018
• Date Completed: 05/05/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-003138-17/results