Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

1. Inoperable stage IIIb/IV histologically/cytologically confirmed lung adenocarcinoma
2. EGFR mutation and EML4-ALK translocation negative
3. Patients with evaluable but unmeasurable disease can be included in the phase I study,but disease must be measurable (CT scan must be within 28 days of randomisation) to beincluded in the phase II study
4. ECOG performance status of 0 or 1
5. Life expectancy of at least 12 weeks
6. Age at least 18 years
7. Adequate haematological status:
8. Haemoglobin ≥100g/L
9. Neutrophil count ≥1.5 x 109/L
10. Platelets ≥100 x 109 /L
11. Adequate organ function:
12. Bilirubin ≤1.5 x ULN
13. ALT or AST ≤3 x ULN (≤5 x ULN is acceptable with liver metastases)
14. Creatinine clearance ≥ 60 ml/min (C&G or EDTA)
15. Negative pregnancy test for female patients of child bearing potential.
16. Male subjects and women of child bearing potential must agree to use an acceptablemethod of birth control for the duration of the trial and for 12 months after the lasttrial treatment administration.
17. Ability to understand and provide written informed consent
18. Ability to comply with the requirements of the protocol

Exclusion Criteria:

1. Prior chemotherapy, hormonal therapy, radiotherapy (including palliativeradiotherapy), immunotherapy or treatment with an investigational drug for advancedNSCLC.
2. Any surgical procedure in the previous 6 weeks prior to registration/ randomisation
3. Known respiratory failure with baseline resting SpO2 <88%
4. Long term oxygen therapy
5. Severe intercurrent infection
6. Active or infected wounds
7. Yellow fever vaccination within 30 days prior to trial registration/randomisation
8. Subject has known sensitivity to any of the trial drugs to be administered during thetrial.
9. Any contraindication to the administration and use of cisplatin, pemetrexed, vitaminB12 or folic acid
10. Prior malignancy other than NSCLC (except if the tumour was a non-melanoma skin tumourthat has been completely excised or in situ cervix carcinoma), unless have beentreated with curative intent with no evidence of disease for > 3 years
11. Evidence of symptomatic brain metastases requiring treatment
12. Myocardial infarction, or unstable or uncontrolled disease or condition related to orimpacting cardiac function (e.g., unstable angina, congestive heart failure [New YorkHeart Association > class II]) within 1 year of enrolment
13. Known inflammatory bowel disease
14. Known hepatitis B or C infection, human immunodeficiency virus (HIV)-positive patients
15. Pregnant women or those who are breast feeding
16. Other medications, severe acute/chronic medical or psychiatric condition, orlaboratory abnormality that may increase the risk associated with trial participationor trial drug administration, or may interfere with the interpretation of trialresults, and in the judgment of the investigator would make the patient inappropriatefor entry into this trial