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 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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 patients with locally advanced or metastatic NSCLC after failure of 1st line anti-cancer therapy;Secondary Objective: To demonstrate, for ZACTIMA in combination with docetaxel compared with docetaxel plus placebo: - An improvement in overall survival - An improvement in the overall objective response rate (ORR) (complete response [CR] + PR), disease control rate (DCR) (CR + PR + Stable Disease [SD] =6 weeks) and duration of response (DOR) using modified RECIST - A beneficial effect on disease-related symptoms based on the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) lung cancer subscale (LCS) - A quality of life (QoL) by assessment of the FACT-L and the Trial Outcome Index (TOI) - An improvement in time to deterioration of disease-related symptoms (TDS) based on the FACT-L LCS To study, in this patient population: - the tolerability and safety, - the population pharmacokinetics - the PK-QTc relationship, - PK-safety relationship - PK-efficacy relationship - Plasma levels of the N-desmethyl and N-oxide metabolites ;Primary end point(s): Progression free survival | — |
Countries
Austria, Belgium, Denmark, Germany, Greece, Italy, Portugal, Spain
Outcome results
None listed