Clinical Trials /

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

NCT02531737

Description:

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.

Related Conditions:
  • Bronchioloalveolar Carcinoma
  • Neuroendocrine Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nintedanib (Vargatef®) Plus Docetaxel in Second Line of Treatment in Patients With Lung Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: I14041/REFRACT
  • NCT ID: NCT02531737

Conditions

  • Lung Neoplasms

Interventions

DrugSynonymsArms
vargatef®Nintedanibtraitment
DocetaxelTaxoteretraitment

Purpose

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 .
    

Trial Arms

NameTypeDescriptionInterventions
traitmentExperimentalPatients 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
  • vargatef®
  • Docetaxel

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:median progression free survival
Time Frame:12 weeks
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital, Limoges

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