Clinical trial NCT02531737: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Neoplasms
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2015-08-24
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: median progression free survival
timeFrame: 12 weeks
Secondary outcomes:
measure: median progression free survival
timeFrame: 12 month
measure: Toxicity (NCIC-CTC version 4.0 criteria)
timeFrame: Every 3 weeks during treatment up to 12 months from inclusion
measure: Quality of life (EQ5-D questionnaire)
timeFrame: every 6 weeks up to 12 months from inlcusion
measure: Response rate
timeFrame: 12 month
Other outcomes:
Locations:
city: Beauvais
country: France
facility: CH de Beauvais
city: Brest
country: France
facility: CHU Brest
city: Créteil
country: France
facility: Service de Pneumologie
city: Gap
country: France
facility: Service de Pneumologie
city: Limoges
country: France
facility: CHU de Limoges
city: LOrient
country: France
facility: CH de Bretagne Sud
city: Mantes La Jolie
country: France
facility: Centre Hospitalier F. Quesnay
city: Marseille
country: France
facility: AP-HM
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Saint Etienne
country: France
facility: Instiut de Cancérologie
city: Villefranche
country: France
facility: Service de Pneumologie
Study officials:
affiliation: CHU LImoges
name: Alain Vergnenegre, MD
role: PRINCIPAL_INVESTIGATOR
References: