Nintedanib (Vargatef®) Plus Docetaxel in Second Line of Treatment in Patients With Lung Cancer

Inclusion Criteria:

* Histologically confirmed non-squamous NSCLC,
* Metastatic NSCLC of stage IV (according to American Joint Committee on Cancers) or recurrent NSCLC)
* Patients without activating epidermal growth factor receptor (EGFR) mutation
* Patients without anaplastic lymphoma kinase (ALK) rearrangement
* Patients must have measurable lesion by RECIST 1.1
* Refractory disease defined by documented progression during the first-line chemotherapy based on a platinum doublet and third-generation drug (four or less cycles) according to RECIST V.1.1
* Age ≥18 years and \< 75 years
* Performance status (PS) 0-1
* Life expectancy of more than 12 weeks.
* No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
* Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to randomization: Normal hepatic function: bilirubin \< 1.5 x N, ALT (alanine transaminase) and AST (aspartate aminotransferase ) \< 2.5 x N or \<5 x N in case of liver metastasis
* Normal renal function (calculated creatinine clearance ≥ 45 mL/min).
* Normal Calcemia
* Normal haematological function (polynuclear neutrophils \> 1.5 G/l, platelets \> 100 G/l).
* Anticoagulation with a vitamin K antagonist and low-molecular-weight heparin (LMWH) is authorized.
* Antiplatelet treatment (aspirin authorized if \< 325 mg/d)
* Treatment with dipyridamole, ticlopidine, clopidogrel is not authorized
* Women of child bearing potential must use double effective contraception.
* Men might be surgically sterile or accept to use an effective contraceptive procedure during and until 6 months after the treatment.
* Written informed consent to participate in the study.

Exclusion Criteria:

* Known hypersensitivity to the trial drugs (nintedanib (vargatef®), docetaxel), peanut, soya, to their excipients
* Controlled disease after first line treatment
* Contra indication to the use of the backbone treatment
* Patients who were withdrawn from first line treatment due to toxicity without documented disease progression or who received placebo (in the context of a clinical trial) as prior treatment are not eligible.
* Previous treatment with docetaxel
* Small-cell lung cancer, bronchioloalveolar cancer, neuroendocrine cancer.
* Previous therapy with vascular endothelial growth factor (VEGF) inhibitors except bevacizumab
* Centrally located tumour with radiographic evidence of local invasion of local blood vessels
* Radiographic evidence of cavitary or necrotic tumours at screening
* Chemo-, hormone-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug.
* Toxicity non resolute due to prior treatment \> grade I (except alopecia).
* Radiotherapy (except extremities) within the past 3 months prior to baseline imaging
* Persistence of clinically relevant therapy related toxicity from previous radiotherapy
* 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 inclusion).
* Uncontrolled arterial hypertension.
* Concurrent radiotherapy, except for palliative bone irradiation.
* Other concurrent severe illnesses (congestive heart failure, unstable angina, significant arrhythmia or myocardial infarction less than 12 months before study entry).
* Stroke less than 6 months before study entry.
* Psychiatric or neurological disorders preventing the patient from understanding the nature of the trial
* Grade \>=1 peripheral neuropathy
* Uncontrolled infection.
* Caval syndrome
* Other organic disorders preventing inclusion in the trial
* Malabsorption syndrome
* Pregnancy and breast-feeding
* Surgery less than two months before study entry.
* Follow-up not feasible.
* Incarcerated and institutionalized