E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
A type of lung cancer at advanced stage |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 bevacizumab treatment beyond PD1 as measured by overall survival (OS). |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy as measured by rate of 6-, 12-, and 18-month OS as measured from randomization at 1st progression of disease (PD1).
• To assess the efficacy as measured by progression free survival (PFS) and time to progression (TTP) from randomization at PD1, to second (2nd) PD (PD2) (PFS2, TTP2), and to third (3rd) PD (PD3)
• To assess the efficacy as measured by response rates (RRs), disease control rates, and duration of response at PD2 and PD3.
• To assess the efficacy in the subgroup of adenocarcinoma patients.
• To assess the safety of bevacizumab treatment across multiple lines of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients, age >/=18 years
- Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC)
- Documented progression of disease (locally recurrent or metastatic) per investigator assessment following first-line treatment 4-6 cycles of Avastin plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Avastin (monotherapy) maintenance treatment prior to first progression of disease
- No treatment interruption of Avastin treatment greater than 2 consecutive cycles (42 days) between the start of first-line treatment to start of Cycle 1 of second line treatment
- Randomization within 4 weeks of progression of disease
- At least one unidimensionally measurable lesion meeting RECIST criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 |
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E.4 | Principal exclusion criteria |
- Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component
- History of pulmonary hemorrhage/hemoptysis greater than or equal to grade 2 within 3 months of randomization
- Major 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 |
Measured from randomization to occurrence of event (death) |
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E.5.2 | Secondary end point(s) |
The rate of 6-, 12-, and 18-month OS as measured from randomization at progression PD1
PFS and TTP from randomization at progressive disease 1 (PD1), to PD2 (Progression Free Survival 2, Time to disease progression 2), and to PD3
Response rates, disease control rates, and duration of response at PD2 and PD3 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measured from randomization and time of progressive disease 2 (PD2) to occurrence of event |
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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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Argentina |
Austria |
Brazil |
Denmark |
France |
Germany |
Greece |
Italy |
Japan |
Lebanon |
Mexico |
Netherlands |
Oman |
Qatar |
Slovakia |
Spain |
United Arab Emirates |
United States |
Jordan |
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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
|
End of trial is defined as the completion of observation period (i.e. when 416 deaths have been reported, or 60 months from study start, whichever occurs first. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |