BIBF 1120 in Combination With Pemetrexed in Advanced Non Small Cell Lung Cancer (NSCLC)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: BIBF 1120 M + Pemetrexed; BIBF 1120 H + Pemetrexed; BIBF 1120 RD + Pemetrexed; BIBF 1120 L + Pemetrexed; BIBF 1120 Placebo + Pemetrexed
Intervention description: BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m^2; BIBF 1120 high dose bid+ Pemetrexed 500 mg/m^2; confirmed dose of BIBF 1120 bid + Pemetrexed 500 mg/m^2; BIBF 1120 low dose bid+ Pemetrexed 500 mg/m^2; placebo BIBF 1120 bid + Pemetrexed 500 mg/m^2
Intervention MeSH terms: Pemetrexed; Nintedanib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 19.0
Sex: All
Minimum age: 20 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The objectives of this trial are to estimate the following in Japanese patients with advanced
      NSCLC of stage IIIB/IV or with recurrence after failure of first-line chemotherapy.

      Phase I part The objective of the phase I part is to define the Maximum Tolerated Dose (MTD)
      of BIBF 1120 at a dose level up to twice daily 200 mg with standard dose of pemetrexed (500
      mg/m^2) and to determine the Recommended Dose (RD) for the phase II part.

      Phase II, to investigate the efficacy and safety of BIBF 1120 in combination with pemetrexed
      (500 mg/m^2) as compared to pemetrexed (500 mg/m^2) + placebo
    

Eligibility criteria:

        Inclusion criteria:

          1. Male or female patients of age >=20 and <=74 years at informed consent

          2. Histologically or cytologically confirmed, Non Small Cell Lung Cancer (NSCLC) of stage
             IIIB or IV or recurrent NSCLC

          3. Relapse or failure of 1 first-line prior chemotherapy

          4. Life expectancy of at least 3 months

          5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

          6. Patients who have sufficient baseline organ function over 4 weeks and whose laboratory
             data meet the following criteria at the enrolment

               -  Haemoglobin >=9.0 g/dL

               -  Absolute neutrophil count (ANC) >=1500/mm^3

               -  Platelet count >=100 000/mm^3

               -  Total bilirubin under the upper limit of normal

               -  AST/SGOT and/or ALT/GPT <=1.5 x upper limit of normal (if related to liver
                  metastases <=2.5 x upper limit of normal also)

               -  Proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or
                  less

               -  Calculated creatinine clearance by Cockcroft Gault >=45 mL/min

               -  Prothrombin time-international normalized ratio (PT-INR) and/or partial
                  thromboplastin time (PTT) greater than 50% deviation from normal limits

               -  arterial oxgen pressure (PaO2) >=60 torr or oxygen saturation by pulse-oximeter
                  SpO2 >=92%

          7. Patient has given written informed consent which must be consistent with ICH-GCP and
             local legislation.

        Exclusion criteria:

          1. Patients who have received treatment with other investigational drugs or treatment in
             another clinical trial within the past 4 weeks before start of therapy or
             concomitantly with this trial or who have not recovered from side effects of such
             therapy (except for alopecia)

          2. Patients who have received chemo-, hormone-, immunotherapy or therapy with monoclonal
             antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to
             treatment with the trial drug or who have not recovered from side effects of such
             therapy (except for alopecia) .

          3. Patients who have received radiotherapy within the following period Phase I part: the
             past 4 weeks prior to treatment with the trial drug (in case of palliative
             radiotherapy such as for extremities, within the past 2 weeks prior to treatment with
             the trial drug)

          4. Previous therapy with other vascular endothelial growth factor receptor (VEGFR)
             inhibitors or vascular endothelial growth factor (VEGF) ligand inhibitors for
             treatment of NSCLC

          5. Previous therapy with BIBF 1120 and/or pemetrexed for treatment of NSCLC and any
             contraindications for therapy with pemetrexed

          6. Patients who have active brain metastases

          7. Leptomeningeal disease

          8. Patients with distinct or suspected pulmonary fibrosis or interstitial lung disease by
             the CT findings, or patients with a previous history of pulmonary fibrosis or
             interstitial lung disease (except irradiation-pneumonitis appearing radiation field
             with past radiotherapy).

          9. Radiographic evidence of cavitary or necrotic tumors

         10. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
             major blood vessels

         11. History of clinically significant haemoptysis within the past 3 months

         12. History of major thrombotic or clinically relevant major bleeding event in the past 6
             months

         13. Known inherited predisposition to bleeding or thrombosis

         14. Significant cardiovascular diseases

         15. Significant weight loss (>10%) within the past 6 weeks prior to treatment in the
             present trial

         16. Current peripheral neuropathy CTCAE grade 2 or greater except due to trauma

         17. Pre-existing ascites and/or clinically significant pleural effusion

         18. Major injuries and/or surgery within the past 4 weeks prior to randomisation with
             incomplete wound healing

         19. Clinically serious infections

         20. Decompensated diabetes mellitus

         21. Contraindication to high dose steroid therapy

         22. Gastrointestinal disorders or abnormalities that would interfere with absorption of
             the study drug

         23. Patients who have active or chronic hepatitis C and/or B infection and diagnosis of
             human immunodeficiency virus (HIV) infection

         24. Other malignancy other than basal cell skin cancer, carcinoma in situ or intra-mucosal
             cancer that were judged to be cured by adequate treatment and disease-free interval is
             more than 5 years

         25. History of serious drug hypersensitivity

         26. Serious illness or concomitant non-oncological disease such as neurologic-,
             psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or
             laboratory abnormality that may increase the risk associated with study participation

         27. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed
             for maintenance of an indwelling intravenous device) or antiplatelet therapy

         28. Patients who are sexually active and unwilling to use a medically acceptable method of
             contraception

         29. Pregnancy or breast feeding

         30. Active alcohol or drug abuse

         31. Patients unable to comply with the protocol

         32. Other patients judged ineligible for enrolment in the study by the investigator or
             subinvestigator.