Lume Lung 2 : BIBF 1120 Plus Pemetrexed Compared to Placebo Plus Pemetrexed in 2nd Line Nonsquamous NSCLC

• overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• tumor response according to modified RECIST criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• incidence and intensity of adverse events according to the common terminology criteria for adverse events (CTCAE version 3.0) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• clinical improvement [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• changes in safety laboratory parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• quality of life measurement (EQ-5D, EORTC, QLQ C-30, EORTC QLQ LC 13) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• pharmacokinetics of BIBF 1120 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

The trial will be performed to evaluate if BIBF 1120 in combination with standard pemetrexed therapy is more effective than placebo (inactive capsule) plus standard pemetrexed therapy in patients with stage IIIB, IV or recurrent NSCLC. Safety information about BIBF1120/pemetrexed will be obtained.

• Drug: Pemetrexed
  500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
• Drug: Folic Acid
• Drug: Placebo plus pemetrexed
  500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
• Drug: BIBF1120
• Drug: BIBF1120 plus pemetrexed
• Drug: Folic Acid
  400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.

• Experimental: BIBF 1120 plus pemetrexed
  BIBF 1120 along with standard therapy of pemetrexed
  Interventions:

  • Drug: Folic Acid
  • Drug: BIBF1120
  • Drug: BIBF1120 plus pemetrexed
• Active Comparator: Placebo plus pemetrexed
  Pemetrexed standard therapy
  Interventions:

  • Drug: Pemetrexed
  • Drug: Placebo plus pemetrexed
  • Drug: Folic Acid

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