E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of continuous treatment with bevacizumab + SOC vs. placebo + SOC beyond 1st PD (PD1) as measured by overall survival (OS) from randomization at PD1 |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Have provided written informed consent.
• 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.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When 250 events have been observed |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at the time of the primary endpoint (when 250 events have been observed) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Health related Quality of Life, Neurocognitive function |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Albania |
Austria |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
China |
Croatia |
Denmark |
Egypt |
Estonia |
Finland |
France |
Greece |
India |
Ireland |
Italy |
Latvia |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Netherlands |
Norway |
Portugal |
Serbia |
Spain |
Sweden |
Turkey |
United Kingdom |
Uruguay |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date when the LPLV occurs. LPLV is planned 30 days after the 250th OS event is reported which is estimated approximately 56 months after the FPI. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |