E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non small cell lung cancer NSCLC |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
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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 demonstrate an improvement in progression-free survival PFS in the combination of ZACTIMA ZD6474 with docetaxel compared with docetaxel plus placebo in subjects with locally advanced or metastatic NSCLC after failure of 1st line anti-cancer therapy. |
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E.2.2 | Secondary objectives of the trial |
1.To demonstrate an improvement in overall survival for ZACTIMA in combination with docetaxel compared with docetaxel plus placebo 2.To demonstrate an improvement in the overall objective response rate ORR complete response CR partial response PR , disease control rate DCR CR PR Stable Disease SD 8805; 6 weeks and duration of response DOR for ZACTIMA in combination with docetaxel compared with docetaxel plus placebo using modified Response Evaluation Criteria in Solid Tumors RECIST Therasse et al, 2000 3.To demonstrate a beneficial effect on disease-related symptoms, in subjects treated with ZACTIMA in combination with docetaxel, that is at least as good as those in subjects treated with docetaxel plus placebo based on the Functional Assessment of Cancer Therapy for Lung Cancer FACT-L lung cancer subscale LCS |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Provision of informed consent 2. Female or male aged 18 years and over 3. Histologic or cytologic confirmation of locally advanced or metastatic NSCLC IIIb-IV on entry into study 4. Failure of 1st line anti-cancer therapy either radiological documentation of disease progression or due to toxicity or subsequent relapse of disease following 1st line therapy 5. WHO PS 0 1 6. One or more measurable lesions at least 10 mm in the longest diameter LD by spiral CT scan or 20 mm with conventional techniques according to RECIST criteria 7. Negative pregnancy test for women of childbearing potential 8. Life expectancy of 12 weeks or longer |
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E.4 | Principal exclusion criteria |
1.Mixed small cell and non-small cell lung cancer histology 2.Subjects who have received 2nd-line anti-cancer therapy 3.Prior treatment with docetaxel prior treatment with paclitaxel is acceptable 4.Prior treatment with VEGFR TKIs previous treatment with bevacizumab Avastin is permitted 5.The last dose of prior chemotherapy or other anti-cancer therapy is discontinued less than 4 weeks before the start of study therapy 6 weeks for nitrosoureas, mitomycin, and suramin 6.The last radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation 7.Any unresolved toxicity CTCAE grade 2 from previous anti-cancer therapy 8.History of arrhythmia multifocal premature ventricular contractions PVCs , bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation which is symptomatic or requires treatment CTCAE grade 3 or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. 9.Presence of left bundle branch block LBBB 10.QTc with Bazett s correction unmeasurable or 8805;480 msec on screening ECG Note If a subject has QTc interval 8805;480 msec on screening ECG, the screen ECG may be repeated twice at least 24 hours apart . The average QTc from the three screening ECGs must be 480 msec in order for the subject to be eligible for the study. 11.Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 10 days |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to demonstrate an improvement in PFS in the combination of ZACTIMA with docetaxel compared with docetaxel plus placebo in subjects with locally advanced or metastatic NSCLC after failure of 1st line anti-cancer therapy |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |