A Phase III, Randomized, Double-blinded, Parallel Group, Multi-centreStudy to Assess the Efficacy and Safety of ZD6474 (ZACTIMA™) inCombination with Pemetrexed (Alimta®) versus Pemetrexed alone inPatients with Locally-Advanced or Metastatic (stage IIIB or IV) Non-SmallCell Lung Cancer (NSCLC) after Failure of 1st Line Anti-cancer Therapy

Phase 1

Conditions: ocally-advanced or Metastatic (stage IIIB or IV) Non-Small Cell Lung Cancer (NSCLC).
MedDRA version: 8.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOS

Registration Number: EUCTR2006-003695-35-GB

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 510

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

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 109/L or platelets <100 x 109/L
10. Serum bilirubin >1.5 x the upper limit of reference range (ULRR)
11. Creatinine clearance <50 ml/min calculated by either Cockcroft –Gault, 24 hours
urine collection, EDTA scan or other validated methods
12. 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
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 (or 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 Appen