Locally-advanced or Metastatic (stage IIIB or IV) Non-Small Cell Lung Cancer (NSCLC). MedDRA version: 8.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Female or male aged 18 years or above 3. Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (stage IIIB or 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 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. Previously irradiated lesions will not be considered measurable. 7. Life expectancy of 12 weeks or longer 8. Negative pregnancy test for women of childbearing potential only For inclusion in this genetic research, patients must fulfil the following criterion: 1. Provision of informed consent for the genetic research 2. Provision of informed consent for tissue research 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 have received 2nd-line or subsequent anti-cancer therapy 3. Prior treatment with pemetrexed 4. Prior treatment with VEGFR TKIs (previous treatment with bevacizumab [Avastin] is permitted) 5. Known or suspected brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 10 days 6. The last radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation 7. The last dose of prior chemotherapy or other anti-cancer therapy is discontinued less than 3 weeks before the start of study therapy (6 weeks for nitrosoureas, mitomycin, and suramin) 8. Major surgery within 4 weeks before entry, or incompletely healed surgical incision 9. Neutrophils 1.5 x the upper limit of reference range (ULRR) 11. Creatinine clearance 2.5 x ULRR in the absence of liver metastases, or > 5 x ULRR in the presence of liver metastases 13. Alkaline phosphatase (ALP) >2.5 x ULRR in the absence of liver metastases, or >5 x ULRR in the presence of liver metastases 14. Current active gastrointestinal disease that may affect the ability of the patient to absorb ZD6474 or tolerate diarrhoea 15. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol 16. Any unresolved toxicity greater than CTCAE Grade 2 from previous anti-cancer therapy 17. Significant cardiovascular event (e.g., myocardial infarction, superior vena cava [SVC] syndrome), New York Heart Association [NYHA] classification of heart disease > 2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia 18. 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 19. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age 20. QT prolongation with other medications that required discontinuation of that medication 21. Presence of left bundle branch block (LBBB) 22. QTc with Bazett’s correction unmeasurable or = 480 msec on screening ECG (Note: If a patient has QTc interval = 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 QTc prolongation (see Appendix D, Table 2) are eligible if QTc is <460 msec. 23. Potassium <4.0 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin), or magnesium out of normal range despite supplementation 24. Women who are pregnant or breast feeding 25. Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see App
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate an improvement in PFS as assessed by RECIST criteria, for the combination of ZD6474 plus pemetrexed (Alimta®) compared with pemetrexed plus placebo in patients with locally advanced or metastatic NSCLC after failure of 1st line anti-cancer therapy (not including an adjuvant regimen). ;Secondary Objective: Demonstrate improvement in overall survival for ZD6474 in combination with pemetrexed compared with pemetrexed plus placebo 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] = 6 weeks) and duration of response (DOR), assessed by RECIST criteria Demonstrate a beneficial effect on disease-related symptoms, based on the Lung Cancer Symptom Scale (LCSS) Demonstrate an improvement in time to deterioration of disease-related symptoms (TDS) To study the tolerability and safety of ZD6474 in combination with pemetrexed by assessment of AEs, clinically significant laboratory or vital signs abnormalities and ECG changes Investigate the population pharmacokinetics (PK) of ZD6474 in this patient population and assess the PK-QTc relationship, PK-safety relationship, PK-efficacy relationship and PK-PD relationship by evaluation of appropriate PK parameters ;Primary end point(s): Primary outcome variable: - Improvement in progression-free survival (PFS) for the combination of ZD6474 plus pemetrexed (Alimta®) compared with pemetrexed plus placebo. | — |
Countries
Belgium, France, Germany, Greece, Italy, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed