Non-small cell lung cancer
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
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. (Sputum cytology alone is not acceptable. Cytology specimens obtained by brushing, washing or needle aspiration are acceptable.) 4. Failure of prior therapy (during or after treatment) with an EGFR TKI (either radiological documentation of disease progression or due to toxicity) in patients who have received at least one but no more than two prior chemotherapy regimens. 5. WHO Performance status 0 – 2 6. Measurable disease defined as - 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 7. Negative pregnancy test for women of childbearing potential 8. Life expectancy of 12 weeks or longer 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Mixed small cell and non–small-cell lung cancer histology 2. Prior treatment with VEGFR TKIs (prior treatment with bevacizumab [Avastin] is permitted) 3. Chemotherapy or other systemic anti-cancer therapy within 4 weeks before the start of study therapy (6 weeks for nitrosoureas, mitomycin and suramin) 4. Three or more prior chemotherapy regimens for advanced disease (one additional regimen allowed for neoadjuvant or adjuvant therapy). 5. The last radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation. 6. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy 7. Any unresolved toxicity > CTCAE grade 2 from previous anti-cancer therapy 8. Serum bilirubin >1.5 x ULRR 9. Serum creatinine >1.5 x ULRR or creatinine clearance =50 ml/min (calculated by Cockcroft-Gault formula [see Appendix G]) 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR in the absence of liver metastases, or >5 x ULRR in the presence of liver metastases 11. Alkaline phosphatase (ALP) >2.5 x ULRR in the absence of liver metastases, or >5 x ULRR in the presence of liver metastases 12. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome), New York Heart Association [NYHA] classification of heart disease ³2 [See Appendix H]) within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia 13. 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. 14. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age 15. QT prolongation with other medication that required discontinuation of that medication 16. Presence of left bundle branch block (LBBB) 17. QTc with Bazett’s correction unmeasurable or = 480 msec or greater on screening ECG. (Note: If a patient has QTc =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 160 millimetre of mercury [mmHg] or diastolic blood pressure >100 mmHg) 23. Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of the skin 24. Evidence of severe or uncontrolled systemic disease or any concurrent condition (e.g. drug or alcohol abuse), which in the Inve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary outcome variable of this study is "overall survival" (OS)which is defined as the number of days from randomisation to death from any cause. ;Main Objective: To demonstrate an improvement in overall survival for ZD6474 (ZACTIMA™ ) plus best supportive care (BSC) compared with placebo plus BSC in patients with locally advanced or metastatic NSCLC after prior therapy with an EGFR TKI;Secondary Objective: To demonstrate an improvement in progression-free survival (PFS) for ZD6474(ZACTIMA) plus BSC compared with placebo plus BSC 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] = 8 weeks) and duration of response (DOR) for ZD6474 plus BSC compared with placebo plus BSC using Response Evaluation Criteria in Solid Tumours (RECIST) To study the safety and tolerability of ZD6474 plus BSC compared with placebo plus BSC To demonstrate beneficial effects in time to deterioration of disease-related symptoms (TDS) assessed by the combined score of LCS, pain and fatigue for ZD6474 plus BSC compared with placebo plus BSC" | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed