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

Phase 1

• Conditions: Glioblastoma; MedDRA version: 18.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003138-17-ES
• Lead Sponsor: Roche Farma, S.A en nombre de F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-16
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

? Are currently enrolled in Study MO28347 and have provided additionl consent following amendment 6 to the protocol, which changed the study from a Phase IIIb to A Phase II study.
? Age ? 18 years .
? Karnofsky performance status (KPS) ? 60.
? Newly diagnosed GBM
? Craniotomy or intracranial biopsy site must be adequately healed. Study treatment should be initiated > 28 days and ? 49 days following the last surgical procedure.
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.
-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 234
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

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 (i.e. anti-VEGF or VEGFR therapies or tyrosine kinase inhibitors).
? Evidence of recent brain haemorrhage
? Acute cardiac disease
?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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of addition of continuous multiple line<br>bevacizumab treatment to lomustine in 2nd-line followed by standard of<br>care (SOC) in 3rd-line and beyond compared to addition of bevacizumab/placebo,<br>as measured by overall survival (OS) from randomisation at<br>first progression of disease (PD1).;Secondary Objective: To assess:<br>? overall survival as measured from randomization at PD1.<br>? progression free survival from randomization at PD1, to 2nd PD (PD2) (PFS2), and to 3rd PD (PD3) (PFS3).<br>? response rates (RRs), disease control rates (DCRs), and durations of response at PD2 and PD3.<br>? the safety of bevacizumab treatment across multiple lines of treatment and from randomization at PD1.<br>? HRQoL, neurocognitive function (NCF) and resource utilization;Primary end point(s): Overall survival (OS);Timepoint(s) of evaluation of this end point: When 130 events have been observed

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - 2nd and 3rd line progression free survival (PFS)<br>- Response, duration of response and disease control rates in 2nd and 3rd line<br>- Safety<br>- Neurocognitive function, Health Related QoL, resource utilization;Timepoint(s) of evaluation of this end point: at the time of the primary endpoint (when 130 events have been observed)