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

Study Overview
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Brief Summary
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The purpose of this study is to determine whether nintedanib (vargatef®) combined with docetaxel are effective in second line of treatment in patients with no squamous non small cell lung cancer refractory to first line chemotherapy.

Detailed Description
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59 Patients with histologically documented stage IV NSCLC no squamous, after failure of first line chemotherapy and refractory (progressive disease during first line chemotherapy), will be enroled to receive docetaxel :75 mg/m² IV day 1 every 3 weeks with nintedanib (vargatef®):200 mg X 2/day per os day2-day21. Tumor response (according to RECIST) will be assessed via computed tomography or magnetic resonance imaging scan every 6 weeks (evaluation of PFS) following completion of chemotherapy. Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria, version 4.0 Quality of life(EQ5-D ) will be assessed every 6 weeks during chemotherapy. Tolerability will be assessed at each visit based on Common Terminology Criteria for Adverse Events (CTCAE), v4.0 criteria. Total study duration per patient: approximately 12 months .

Official Title
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Multicenter Phase II Trial of Nintedanib (Vargatef®) Plus Docetaxel in Second Line of Treatment in Patients With no Squamous Non Small Cell Lung Cancer Refractory to First Line Chemotherapy

Conditions
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Lung Neoplasms

Intervention / Treatment
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* Drug: vargatef®
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: traitment<br>Patients will be treated to oral nintedanib (vargatef®) 400 mg/d on days 2 to 21 of a 3-week cycle including docetaxel 75 mg/m2 by intravenous infusion on day 1 | Drug: vargatef®<br>* Patients will be treated to oral nintedanib (vargatef®) 400 mg/d on days 2 to 21 of a 3-week cycle<br>* Other names: Nintedanib;Drug: Docetaxel<br>* Patients will be treated to IV docetaxel 75 mg/m² on day 1 of evry 3-week cycle<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median progression free survival |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median progression free survival |  | 12 month | 
| Toxicity (NCIC-CTC version 4.0 criteria) |  | Every 3 weeks during treatment up to 12 months from inclusion | 
| Quality of life (EQ5-D questionnaire) |  | every 6 weeks up to 12 months from inlcusion | 
| Response rate |  | 12 month |