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

Lung Neoplasms Clinical Trial

— REFRACT  

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 Details — Status: Completed

Administrative data

• NCT number: NCT02531737
• Other study ID #: I14041/REFRACT
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: September 26, 2020

Study information

• Verified date: July 2019
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: September 26, 2020
• Est. primary completion date: September 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Lung Neoplasms

Intervention

Drug:
• vargatef®
Patients will be treated to oral nintedanib (vargatef®) 400 mg/d on days 2 to 21 of a 3-week cycle
• Docetaxel
Patients will be treated to IV docetaxel 75 mg/m² on day 1 of evry 3-week cycle

Locations

Country	Name	City	State
France	CH de Beauvais	Beauvais
France	CHU Brest	Brest
France	Service de Pneumologie	Créteil
France	Service de Pneumologie	Gap
France	CHU de Limoges	Limoges
France	CH de Bretagne Sud	LOrient
France	Centre Hospitalier F. Quesnay	Mantes La Jolie
France	AP-HM	Marseille
France	Institut Paoli-Calmettes	Marseille
France	Instiut de Cancérologie	Saint Etienne
France	Service de Pneumologie	Villefranche

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Limoges	Boehringer Ingelheim

Country where clinical trial is conducted

France, 

Outcome

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