A Randomized Double-blind Multicenter Phase III Trial of BIBF 1120 Plus Pemetrexed vs. Pemetrexed/ Placebo in Advanced or Recurrent Non Small Cell Lung Cancer Patients After Failure of First Line Therapy

Inclusion Criteria

Inclusion criteria:

1. Male or female patient aged 18 years or older.

2. Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or
recurrent NSCLC (non squamous histologies)

3. Relapse or failure of one first line chemotherapy (in the case of recurrent disease
one additional prior regimen is allowed for adjuvant, neoadjuvant or neoadjuvant plus
adjuvant therapy).

4. At least one target tumor lesion that has not been irradiated within the past three
months and that can accurately be measured by magnetic resonance imaging (MRI) or
computed tomography (CT) in at least one dimension (longest diameter to be recorded)
as greater than or equal to 20 mm with conventional techniques or as greater than or
equal to 10 mm with spiral CT.

5. Life expectancy of at least three months.

6. ECOG score of 0 or 1.

7. Patient has given written informed consent which must be consistent with the
International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local
legislation.

Exclusion criteria:

1. Previous therapy with other VEGF inhibitors (other than bevacizumab) or pemetrexed
for treatment of NSCLC

2. Treatment with other investigational drugs or treatment in another clinical trial
within the past four weeks before start of therapy or concomitantly with this trial

3. Chemotherapy, hormone therapy, immunotherapy with monoclonal antibodies, treatment
with tyrosine kinase inhibitors, or radiotherapy (except for treatment of brain and
extremities) within the past four weeks prior to treatment with the trial drug, i.e.,
the minimum time elapsed since the last anticancer therapy and the first
administration of BIBF 1120 must be four weeks

4. Inability to stop intake of NSAIDS (non steroidal anti inflammatory drugs) for
several days

5. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment
with radiotherapy, symptomatic, requiring treatment with anti-convulsants).
Dexamethasone therapy will be allowed if administered as stable dose for at least one
month before randomisation)

6. Radiographic evidence of cavitary or necrotic tumors

7. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
major blood vessels

8. History of clinically significant haemoptysis within the past 3 months

9. Therapeutic anticoagulation

10. History of major thrombotic or clinically relevant major bleeding event in the past 6
months

11. Significant cardiovascular diseases (i.e., hypertension not controlled by medical
therapy, unstable angina, history of myocardial infarction within the past 6 months,

12. Inadequate kidney, liver, blood clotting function

13. Inadequate blood count

14. Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the
present trial

15. Current peripheral neuropathy greater than or equal to CTCAE Grade 2 except due to
trauma

16. Pre-existing ascites (abdominal fluid collection) and/or clinically significant
pleural effusion ( fluid collection between the lung and chest wall)

17. Major injuries and/or surgery within the past ten days prior to start of study drug

18. Incomplete wound healing

19. Active or chronic hepatitis C and/or B infection