Multicenter, randomised, double-blind, Phase III trial to investigate theefficacy and safety of oral BIBF 1120 plus standard pemetrexed therapycompared to placebo plus standard pemetrexed therapy in patients withstage IIIB/IV or recurrent non small cell lung cancer after failure of firstline chemotherapy - BIBF plus Pemetrexed in 2nd line NSCLC patients

• Conditions: Stage IIIB/IV or recurrent non small cell lung cancer. non squamous histology; MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: LLTClassification code 10029522Term: Non-small cell lung cancer stage IV; MedDRA version: 9.1Level: LLTClassification code 10029515Term: Non-small cell lung cancer recurrent

• Registration Number: EUCTR2008-002072-10-RO
• Lead Sponsor: Boehringer Ingelheim International GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1300

Inclusion Criteria

Male or female patient aged 18 years or older
• Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or
recurrent NSCLC (non squamous histologies)
• 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)
• 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 =20 mm with conventional techniques or as =10 mm with spiral CT
• Life expectancy of at least three months
• ECOG score of 0 or 1
• Patient has given written informed consent which must be consistent with the
International Conference on Harmonization – Good Clinical Practice (ICH-GCP) and
local legislation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- More than one prior chemotherapy regimen for advanced and/or metastatic disease of NSCLC
- More than one chemotherapy treatment regimen (either neoadjuvant or adjuvant or neoadjvant plus adjuvant) prior to first line chemotherapy of advanced and/or metastatic NSCLC
- Previous therapy with other VEGFR inhibitors (other than bevacizumab) or
pemetrexed for treatment of NSCLC
- Persistence of clinically relevant therapy related toxicities from previous
chemotherapy and/or radiotherapy
- 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
- Chemo-, hormone-, immunotherapy with monoclonal antibodies, treatment with tyrosine kinase inhibitors, or radiotherapy (except for 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.
- Radiotherapy (except extremities and brain) within the past three months prior to
baseline imaging
- Patients taking NSAIDS with short half lives unable or unwilling to interrupt
NSAIDsS for a five day period (2 days before pemetrexed, day of pemetrexed, 2 days
after pemetrexed)
Patients taking NSAIDS with long half lives must interrupt NSAID for 8 days (5 days
before, day of and 2 days after treatment with pemetrexed)
- 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)
- leptomeningeal disease
- Radiographic evidence of cavitary or necrotic tumors
- Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
major blood vessels
- History of clinically significant haemoptysis within the past 3 months (more than one tea spoon of fresh blood per day)
- Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =?325mg per day)
- History of major thrombotic or clinically relevant major bleeding event in the past
6 months
- Known inherited predisposition to bleeding or thrombosis
- Significant cardiovascular diseases (i.e., hypertension not controlled by medical
therapy, unstable angina, history of myocardial infarction within the past 6 months,
congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
- Calculated creatinine clearance by Cockcroft Gault <45ml/min
- Proteinuria CTCAE grade 2 or greater
- Total bilirubin above the upper limit of normal
- ALT and/or AST > 2.5 x upper limit of normal in the presence of live metastasis or
ALT and/or AST >1.5 x upper limit of normal in patients without liver metastasis.
- Prothrombin time and/or partial thromboplastin time greater than 50% deviation from normal limits
- Absolute neutrophil count (ANC) < 1500 neutrophils /mm3
- Platelets < 100,000 platelets/mm
- Haemoglobin < 9.0 g/dL
- Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the
present trial
Major injuries and/or surgery within the past ten days prior to randomisation with
incomplete wound healing
- Current peripheral neuropathy =?CTCAE grade 2 except due to trauma
- Preexisting ascites and/or cl

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The present trial will be performed to evaluate whether BIBF 1120 in combination with standard therapy pemetrexed in patients with Stage IIIB/IV or recurrent NSCLC is more effective compared to placebo in combination with standard therapy pemetrexed. The trial will be limited to non squamous histologies. ;Secondary Objective: A secondary aim is to obtain safety information as well as information on quality of life of patients treated with BIBF 1120/pemetrexed compared to standard pemetrexed alone. In addition, blood will be collected for pharmacokinetic analysis.;Primary end point(s): progression free survival (imaging assessed by an independent central review<br>according to the modified RECIST criteria)