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). Sputum cytology alone is not acceptable. Cytology specimens obtained by brushing, washing, or needle aspiration are acceptable. 4. Failure of at least one, but no more than two, prior cytotoxic chemotherapy regimens (either radiological documentation of disease progression or due to toxicity). 5. WHO Performance status 0 – 2 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. 9. Able to read and write For inclusion in the genetic research part of the study, patients must fulfil the following criterion: 10. Provision of informed consent for genetic research and tissue sampling 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 EGFR TKIs or VEGFR TKIs (prior treatment with cetuximab [Erbitux] or 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. Radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation. Lesions that have received radiation in the advanced setting cannot be included as target lesions unless clear tumour progression has been documented in the lesions since the end of radiation therapy 5. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy 6. Any unresolved toxicity > CTCAE grade 2 from previous anti-cancer therapy 7. Serum bilirubin greater than 1.5x upper limit of reference range (ULRR) 8. Serum creatinine greater than 1.5 x ULRR or creatinine clearance =30 ml/min (calculated by Cockcroft-Gault formula) See Appendix G. 9. ALT or AST > 2.5 x ULRR if no demonstrable liver metastases, or > 5 x ULRR if judged by the Investigator to be related to liver metastases 10. Alkaline phosphatase (ALP) > 2.5 x ULRR if no demonstrable liver metastases, or > 5 x ULRR if judged by the Investigator to be related to liver metastases 11. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease (see appendix I of protocol) =2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia 12. 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 4) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication, is not excluded. 13. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age 14. QT prolongation with other medications that required discontinuation of that medication 15. Presence of left bundle branch block (LBBB) 16. 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 <480 msec in order for the patient to be eligible for the study). Patients who are receiving a drug that has a risk of QT prolongation (see Appendix D, Table 2) are excluded if QTc is = 460 msec. 17. Potassium <4.0 mmol/L despite supplementation; serum calcium (or ionized or adjusted for albumin), or magnesium out of normal range despite supplementation 18. Women who are pregnant or breast feeding 19. Concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see appendix D). Drugs listed in Appendix D, Table 2, that in the Investigator's opinion cannot be discontinued, are allowed. 20. Concomitant medications that are potent inhibitors (ketoconazole, itraconazole, atanazavir, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO) and voriconazole) or inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate an improvement in Progression Free Survival (PFS) for ZD6474 (ZACTIMA™ ) Versus Erlotinib (Tarceva®) in patients with locally advanced or metastatic NSCLC after failure of at least one but no more than two, prior cytotoxic chemotherapy regimens. ;Secondary Objective: 1. To demonstrate an improvement in overall survival (OS) for ZD6474 compared with Erlotinib 2. To demonstrate an improvement in the objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) for ZD6474 compared with Erlotinib 3. To demonstrate an improvement in the time-to-deterioration of pain, dyspnoea, cough in patients treated with ZD6474, compared with Erlotinib, based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) plus lung cancer module (QLQ-LC13) 4. To study the safety and tolerability of ZD6474 compared with Erlotinib 5. To investigate the population pharmacokinetics (PK) of ZD6474 and assess the relationship between PK and QTc, measures of safety and efficacy and pharmacodynamic (PD) biomarkers. 6. To investigate plasma levels of the N-desmethyl and N-oxide metabolites of ZD6474 in this patient population ;Primary end point(s): Progression free survival | — |
Countries
Denmark, Germany, Italy, Netherlands, Norway, Spain, United Kingdom
Outcome results
None listed