This trial is active, not recruiting.

Condition carcinoma, non-small-cell lung
Treatments bibf 1120 m + pemetrexed, bibf 1120 h + pemetrexed, bibf 1120 rd + pemetrexed, bibf 1120 l + pemetrexed, bibf 1120 placebo + pemetrexed
Phase phase 1
Sponsor Boehringer Ingelheim
Start date October 2009
End date May 2012
Trial size 18 participants
Trial identifier NCT00979576, 1199.28


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/m2) 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/m2) as compared to pemetrexed (500 mg/m2) + placebo

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double-blind
Primary purpose treatment
Phase I part: Find MTD by using low, medium or high BIBF 1120 twice daily and 500mg/m2 pemetrexed once every 3 weeks
bibf 1120 m + pemetrexed
BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m2
bibf 1120 h + pemetrexed
BIBF 1120 high dose bid+ Pemetrexed 500 mg/m2
bibf 1120 l + pemetrexed
BIBF 1120 low dose bid+ Pemetrexed 500 mg/m2
PHase II part: Study arm
bibf 1120 rd + pemetrexed
confirmed dose of BIBF 1120 bid + Pemetrexed 500 mg/m2
Phase II part: Comparator arm
bibf 1120 placebo + pemetrexed
placebo BIBF 1120 bid + Pemetrexed 500 mg/m2

Primary Outcomes

Phase I part: Maximum Tolerated Dose (MTD) in combination therapy of BIBF 1120 and pemetrexed (500 mg/m2) and Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE)
time frame: 4 months
Phase II part: Progression Free Survival (PFS)
time frame: 4 months

Secondary Outcomes

Phase I part: Pharmacokinetic (PK), Tumor response and Safety laboratory parameters
time frame: 4 months
Phase II part: Tumor response, Overall Survival (OS), Clinical improvement, AE according to CTCAE, Safety laboratory parameters, Quality of Life (QOL) and PK
time frame: 4 months

Eligibility Criteria

Male or female participants from 20 years up to 74 years old.

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/mm3 - Platelet count >=100 000/mm3 - 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.

Additional Information

Official title A Phase I/II Study of Continuous, Concomitant Oral Treatment With BIBF 1120 and Pemetrexed - a Phase I, Open-label, Dose-escalation Study & a Phase II, 2 Arm, Randomized, Double-blind, Placebo-controlled Study in Japanese Patients With Stage IIIB/IV or Recurrent Non-small-cell Lung Cancer After Failure of Chemotherapy
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.