Lume Lung 2 : BIBF 1120 Plus Pemetrexed Compared to Placebo Plus Pemetrexed in 2nd Line Nonsquamous NSCLC
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Nintedanib (BIBF1120); Pemetrexed; pemetrexed; B12; dexamethasone (or corticosteroid equivalent); placebo; dexamethasone (or corticosteroid equivalent); B12; Folic Acid; B12; dexamethasone (or corticosteroid equivalent); Folic Acid; placebo; Folic Acid; Nintedanib (BIBF1120); Pemetrexed
Intervention description: starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.; 500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.; 500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.; 1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed; 4 mg PO bid the day before, the day of and the day after each pemetrexed infusion; starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.; 4 mg PO bid the day before, the day of and the day after each pemetrexed infusion; 1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed; 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.; 1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed; 4 mg PO bid the day before, the day of and the day after each pemetrexed infusion; 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.; starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.; 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.; starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.; 500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
Intervention MeSH terms: Folic Acid; Vitamin B Complex; Hydroxocobalamin; Vitamin B 12; Dexamethasone; Dexamethasone acetate; Pemetrexed; Nintedanib; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 718.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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 non small cell lung cancer (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. Eastern Cooperative Oncology Group (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 vascular endothelial growth factor (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 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 Common Terminology Criteria for
             Adverse Events (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 Additional exclusion criteria apply