A comparison of continuous Avastin treatment or placebo in addition to lomustine followed by standard treatment for worsening brain cancer
- Conditions
- GlioblastomaMedDRA version: 17.0Level: 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-LT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 510
• 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 2nd-line 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
• 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
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 bevacizumab treatment to lomustine in 2nd-line followed by standard of care (SOC) in 3rd-line and beyond compared to addition of bevacizumab-placebo, as measured by overall survival (OS) from randomisation at 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 <br>;Primary end point(s): Overall survival (OS);Timepoint(s) of evaluation of this end point: When 250 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 250 events have been observed)