E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non Small cell lung cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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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 |
The primary objective of this Phase IIIb study is to compare PFS in subjects randomized to bevacizumab + erlotinib versus bevacizumab + erlotinib-placebo in subjects with NSCLC who have completed four cycles of chemotherapy and bevacizumab without disease progression or significant toxicity. For the primary objective, PFS is defined as the length of time from randomization until documented disease progression (as assessed according to the Response Evaluation Criteria in Solid Tumors [RECIST; see Appendix C]) or death on study treatment, whichever occurs earlier. Death on study treatment is defined as death from any cause within 30 days of the last dose of study treatment. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: ユ Among all enrolled subjects, to evaluate the safety of bevacizumab during the chemotherapy phase by chemotherapy regimen and overall as measured by the incidence of selected Grade >= 3 adverse events (see secondary outcome measures, Section 3.3.2) ユ Among subjects who complete four cycles of chemotherapy and bevacizumab and undergo randomization, to evaluate the safety of bevacizumab + erlotinib versus bevacizumab + erlotinibplacebo during the post-chemotherapy phase, as measured by the incidence of all adverse events ユ Among all enrolled subjects, to evaluate the safety of bevacizumab for both phases of therapy by chemotherapy regimen and overall as measured by the incidence of selected Grade >= 3 adverse events (see Section 3.3.2) Among all enrolled subjects, to evaluate the incidence of treatment discontinuation for reasons other than disease progression during both phases of therapy ユ Among subjects who complete four cycles of chemoth |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria Subjects must meet the following criteria to be eligible for enrollment: ユ Signed Informed Consent Form ユ Histologically or cytologically confirmed NSCLC Mixed tumors will be categorized by the predominant cell type. Cytologic or histologic elements may be established on metastatic tumor aspirates or biopsy. Advanced NSCLC (Stage IIIB with malignant pleural effusion or Stage IV) or recurrent disease |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be excluded from enrollment: ユ Prior systemic chemotherapy in the metastatic setting Prior adjuvant therapy and prior combined modality therapy is allowed provided that there is an interval of at least 6 months prior to recurrence. Treatment with an investigational or marketed agent that acts by either EGFR inhibition or anti-angiogenesis mechanisms EGFR inhibitors include (but are not limited to) erlotinib, gefitinib, cetuximab, and CI-1033. Angiogenesis inhibitors include (but are not limited to) bevacizumab, thalidomide, CP-547632, sunitinib, and sorafinib. ユ Pregnancy or lactation |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis of bevacizumab + erlotinib compared with bevacizumab + erlotinibplacebo will be evaluated by post-chemotherapy PFS.PFS is defined as the length of time from randomization until documented disease progression or death on study treatment. Disease progression will be determined by tumor measurements recorded and assessed according to RECIST (see Appendix C). Death on study treatment is defined as death from any cause within 30 days of the last dose of study treatment. Tumor measurements from the prerandomization assessment will serve as the baseline for determining progression. The final analysis will be conducted after a minimum of 638 PFS events in both treatment arms have occurred.PFS will be tested using a two-sided stratified log-rank test with an overall α = 0.05. The stratification factors will consist of sex, smoking history (never vs. prior/current), ECOG performance status from pre-randomization assessment (0 vs. >= 1), and initial chemotherapy regimen (carboplatin/paclitaxel vs. carboplatin/gemcitabine vs. carboplatin/docetaxel vs. cisplatin/ gemcitabine vs. other chemotherapy regimens). Results from an unstratified log-rank test will also be presented. Kaplan-Meier methodology will be used to estimate median PFS for each treatment arm. Kaplan-Meier curves will be constructed to provide a visual description of the difference between the two treatment arms. The hazard ratio for PFS will be estimated using a stratified Cox regression model with the same stratification factors used in the stratified log-rank test. The unstratified hazard ratio will also be presented. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |