Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

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

Summary: 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: 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 .

Eligibility: 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

Relevance to patient case: not relevant