A Phase III, Randomized, Double-Blinded, Multi-Centre Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination with ZD6474 (ZACTIMA™) versus Docetaxel (TAXOTERE™) in combination with Placebo in Patients With Locally Advanced or Metastatic (Stage IIIb – IV) Non-small Cell Lung Cancer (NSCLC) after Failure of 1st Line Anti-Cancer Therapy

Conditions: on-small cell lung cancer

Registration Number: EUCTR2005-004749-32-DE

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1380

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 1 st line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following first 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
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

1. Mixed small cell and non-small cell lung cancer histology

2. Patients who have received second-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. Major surgery within 4 weeks, or incompletely healed surgical incision

8. Any unresolved toxicity > CTCAE grade 2 from previous anti-cancer therapy

9. Neutrophils <1.5 x 10e9 /L and/or platelets <100 x 10 e9 /L

10. Serum bilirubin greater than upper limit of reference range (ULRR)

11. Creatinine clearance <30 mL/minute (calculated by Cockcroft-Gault formula [see Appendix G])

12. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 x ULRR or alkaline phosphatase >2.5 x ULRR

13. Significant cardiovascular event (eg. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease 2 [See Appendix L]) within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia

14. 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.

15. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age

16. QT prolongation with other medications that required discontinuation of that medication

17. Presence of left bundle branch block (LBBB)

18. QTc with Bazett’s correction unmeasurable or =480 msec on screening ECG (Note: If a subject has QTc interval =480 msec on screening ECG, the screen ECG may be repeated up to 2 additional times, with each ECG at least 24 hours apart. The average QTc from up to three screening ECGs must be <480 msec in order for the subject to be eligible for the study. Subjects who are receiving a drug that has a risk of QTc prolongation (see Appendix D, Table 2) are excluded if the screening QTc is =460 msec.

19. Potassium <4.0 mmol despite supplementation; serum calcium (ionized or adjusted for albumin), or magnesium out of normal range despite supplementation

20. Women who are pregnant or breast feeding

21. Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see Appendix D for the lists of medications in Table 1 & Table 2) or induce CYP3A4 function (see Section 3.7.2) within 2 weeks of start of study treatment. Drugs listed in Appendix D, Table 2, that in the Investigator’s opinion cannot be discontinued, are allowed (additional criteria must also be met - see Exclusion Criteria #18).

22. Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 10 days

23. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 millimeter of mercury [mmHg] or diastolic blood pressure gre