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

• Status: Completed
• Trial end date: 2020-09-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Limoges
• Collaborator: Boehringer Ingelheim
• Treatments: Docetaxel; Nintedanib

Criteria

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