Carcinoma, Non-Small-Cell Lung
Conditions
Brief 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
Interventions
DRUGBIBF 1120 M + Pemetrexed
BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m\^2
DRUGBIBF 1120 H + Pemetrexed
BIBF 1120 high dose bid+ Pemetrexed 500 mg/m\^2
DRUGBIBF 1120 RD + Pemetrexed
confirmed dose of BIBF 1120 bid + Pemetrexed 500 mg/m\^2
DRUGBIBF 1120 L + Pemetrexed
BIBF 1120 low dose bid+ Pemetrexed 500 mg/m\^2
DRUGBIBF 1120 Placebo + Pemetrexed
placebo BIBF 1120 bid + Pemetrexed 500 mg/m\^2
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities | During the first course, 21 days | Number of participants with dose limiting toxicity (DLT) in combination therapy of BIBF 1120 and pemetrexed during the first course |
| Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days | Number of patients with adverse events according to worst Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE) or 5 (death related to AE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Disease Control | From first study drug administration until PD or death, up to 1003 days | Duration of disease control was defined as the time period from the first study drug administration to the progressive disease (PD) or death of patients, whichever occurred earlier. |
| Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days | Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events which occurred in \>= 20% of patients |
| AUC0-inf of Nintedanib | 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1 | Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) |
| Disease Control Rate | Every 6 weeks after start of study treatment until end of treatment, up to 992 days | Number of participants with complete response (CR), partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 |
| AUC0-inf of Pemetrexed | 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2 | Area under the concentration-time curve of pemetrexed in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) |
| Cmax of Pemetrexed | 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2 | Maximum measured concentration of pemetrexed in plasma (Cmax) |
| Cmax of Nintedanib | 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1 | Maximum measured concentration of nintedanib in plasma (Cmax) |
| Overall Response Rate | Every 6 weeks after start of study treatment until end of treatment, up to 992 days | Number of participants with complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 |
Countries
Japan
Participant flow
Pre-assignment details
19 patients were enrolled in the study however one patient did not meet the inclusion criteria and therefore did not participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses. | 3 |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles.
In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses. | 6 |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles.
In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses. | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Combination Followed by Monotherapy | Progressive Disease | 0 | 2 | 1 |
| Combination Treatment Phase | Adverse Event | 0 | 2 | 2 |
| Combination Treatment Phase | Dose limiting toxicity | 0 | 3 | 2 |
| Combination Treatment Phase | Progressive disease | 3 | 1 | 5 |
Baseline characteristics
| Characteristic | BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Total |
|---|---|---|---|---|
| Age, Continuous | 61.0 years | 66.0 years | 64.0 years | 64.0 years |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 9 / 9 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 | 1 / 9 |
Outcome results
Primary
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses
Number of patients with adverse events according to worst Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE) or 5 (death related to AE).
Time frame: Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 0 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 1 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 5 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 1 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 0 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 1 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 1 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 5 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 2 participants |
Primary
Dose Limiting Toxicities
Number of participants with dose limiting toxicity (DLT) in combination therapy of BIBF 1120 and pemetrexed during the first course
Time frame: During the first course, 21 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Dose Limiting Toxicities | 0 Participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Dose Limiting Toxicities | 1 Participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Dose Limiting Toxicities | 2 Participants |
Secondary
AUC0-inf of Nintedanib
Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time frame: 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1
Population: Pharmacokinetic (PK) set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | AUC0-inf of Nintedanib | 105 ng*h/mL | Geometric Coefficient of Variation 25.5 |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | AUC0-inf of Nintedanib | 232 ng*h/mL | Geometric Coefficient of Variation 60.5 |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | AUC0-inf of Nintedanib | 323 ng*h/mL | Geometric Coefficient of Variation 28.8 |
Secondary
AUC0-inf of Pemetrexed
Area under the concentration-time curve of pemetrexed in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time frame: 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | AUC0-inf of Pemetrexed | Cycle 1 | 194000 ng*h/mL | Geometric Coefficient of Variation 19.9 |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | AUC0-inf of Pemetrexed | Cycle 2 (N=11) | 200000 ng*h/mL | Geometric Coefficient of Variation 15.9 |
Secondary
Cmax of Nintedanib
Maximum measured concentration of nintedanib in plasma (Cmax)
Time frame: 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Cmax of Nintedanib | 20.5 ng/mL | Geometric Coefficient of Variation 31 |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Cmax of Nintedanib | 37.9 ng/mL | Geometric Coefficient of Variation 71.7 |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Cmax of Nintedanib | 55.1 ng/mL | Geometric Coefficient of Variation 29.6 |
Secondary
Cmax of Pemetrexed
Maximum measured concentration of pemetrexed in plasma (Cmax)
Time frame: 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Cmax of Pemetrexed | Cycle 1 | 139000 ng/mL | Geometric Coefficient of Variation 16.5 |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Cmax of Pemetrexed | Cycle 2 (N=11) | 149000 ng/mL | Geometric Coefficient of Variation 15.4 |
Secondary
Disease Control Rate
Number of participants with complete response (CR), partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0
Time frame: Every 6 weeks after start of study treatment until end of treatment, up to 992 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Disease Control Rate | 2 Participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Disease Control Rate | 4 Participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Disease Control Rate | 6 Participants |
Secondary
Duration of Disease Control
Duration of disease control was defined as the time period from the first study drug administration to the progressive disease (PD) or death of patients, whichever occurred earlier.
Time frame: From first study drug administration until PD or death, up to 1003 days
Population: Patients from the treated set who achieved disease control
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Duration of Disease Control | 248.5 Days |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Duration of Disease Control | 228.5 Days |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Duration of Disease Control | 149.0 Days |
Secondary
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters
Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events which occurred in \>= 20% of patients
Time frame: Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 1 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 2 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 0 participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 3 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 1 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 6 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 1 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 1 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 5 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 1 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 2 participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 5 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 3 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 3 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 2 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 4 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 3 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 7 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 8 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 8 participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 4 participants |
Secondary
Overall Response Rate
Number of participants with complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0
Time frame: Every 6 weeks after start of study treatment until end of treatment, up to 992 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Complete response | 0 Participants |
| BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Partial response | 0 Participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Complete response | 0 Participants |
| BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Partial response | 1 Participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Complete response | 0 Participants |
| BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 | Overall Response Rate | Partial response | 1 Participants |