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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02531737
Recruitment Status : Active, not recruiting
First Posted : August 24, 2015
Last Update Posted : July 5, 2019
Boehringer Ingelheim
Information provided by (Responsible Party):
University Hospital, Limoges

Brief 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.

Condition or disease Intervention/treatment Phase
Lung Neoplasms Drug: vargatef® Drug: Docetaxel Phase 2

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 .

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: traitment
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®
Patients will be treated to oral nintedanib (vargatef®) 400 mg/d on days 2 to 21 of a 3-week cycle
Other Name: Nintedanib

Drug: Docetaxel
Patients will be treated to IV docetaxel 75 mg/m² on day 1 of evry 3-week cycle
Other Name: Taxotere

Primary Outcome Measures :
  1. median progression free survival [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. median progression free survival [ Time Frame: 12 month ]
  2. Toxicity (NCIC-CTC version 4.0 criteria) [ Time Frame: Every 3 weeks during treatment up to 12 months from inclusion ]
  3. Quality of life (EQ5-D questionnaire) [ Time Frame: every 6 weeks up to 12 months from inlcusion ]
  4. Response rate [ Time Frame: 12 month ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02531737

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CH de Beauvais
Beauvais, France
CHU Brest
Brest, France
Service de Pneumologie
Créteil, France
Service de Pneumologie
Gap, France
CHU de Limoges
Limoges, France, 87000
CH de Bretagne Sud
LOrient, France
Centre Hospitalier F. Quesnay
Mantes La Jolie, France, 78200
Marseille, France
Institut Paoli-Calmettes
Marseille, France
Instiut de Cancérologie
Saint Etienne, France
Service de Pneumologie
Villefranche, France
Sponsors and Collaborators
University Hospital, Limoges
Boehringer Ingelheim
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Principal Investigator: Alain Vergnenegre, MD CHU LImoges

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Responsible Party: University Hospital, Limoges Identifier: NCT02531737    
Other Study ID Numbers: I14041/REFRACT
First Posted: August 24, 2015    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors