Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Recurrence

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Nintedanib

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

BIBF 1120 2 times daily along with standard therapy of docetaxel

Placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel

placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel

placebo plus docetaxel

BIBF 1120 plus docetaxel

Boehringer Ingelheim

The present trial will be performed to evaluate whether BIBF 1120 in combination with standard therapy of docetaxel in patients with stage IIIB/IV or recurrent NSCLC is more effective as compared to placebo in combination with standard therapy of docetaxel. A secondary aim is to obtain safety information as well as information on quality of life of patients treated with BIBF 1120 in combination to standard therapy with docetaxel. In addition, blood will be collected for pharmacokinetic analysis.

LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in 2nd Line Non Small Cell Lung Cancer

Multicentre, Randomised, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Docetaxel Therapy Compared to Placebo Plus Standard Docetaxel Therapy in Patients With Stage IIIB/IV or Recurrent Non Small Cell Lung Cancer After Failure of First Line Chemotherapy

Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P\<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and \<9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0 for target lesions : Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion.

Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items.

The following were the main points of interest:

Time to deterioration of cough (EORTC QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19).

Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve

Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.

Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.

Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.

Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.

Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).

Nintedanib Plus Docetaxel

Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Placebo Plus Docetaxel

Total

Age, Continuous

Sex: Female, Male

Tumour histology

Randomised patients with adenocarcinoma and time since first line therapy.

Number of patients with adenocarcinoma and time since first line therapy in categories

Randomised Set (RS)- Includes all randomised patients, whether patients had received study treatment or not

Boehringer Ingelheim Call Center

HR, Confidence Interval (CI) and p-value obtained from the proportional hazards model stratified by baseline ECOG PS (0 vs 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)

Progression Free Survival (PFS) as Assessed by Central Independent Review

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and \<9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for patients with adenocarcinoma and \<9 months since start of first line therapy.

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and \<9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for patients with adenocarcinoma.

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and \<9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for all patients.

Adenocarcinoma and <9 months

Adenocarcinoma

All patients

Overall Survival (Key Secondary Endpoint)

Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review

Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator

Analysis based on the central independent review

Analysis based on the investigator's assessment

central independent reviewer

investigator assessment

Objective Tumour Response

Duration of Confirmed Objective Tumour Response

Time to Confirmed Objective Tumour Response

Analysis based on investigator's assessment

Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 (with dose reduction to 60 mg/m2 if required) once every 3 weeks administered via intravenous infusion over 1 hour (h).

Disease Control

Duration of Disease Control

Change From Baseline in Tumour Size

Nitedanib Plus Docetaxel

Clinical Improvement

Analysis evaluating the time to deterioration of cough

Analysis evaluating the time to deterioration of dyspnoea

Analysis evaluating the time to deterioration of pain

Time to deterioration of cough

Time to deterioration of dyspnoea

Time to deterioration of pain

Quality of Life (QoL)

nintedanib

metabolite BIBF 1202

metabolite BIBF 1202 glucuronide

Nitedanib 200 mg Bid Plus Docetaxel

Nintedanib 150 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Nintedanib 150 Bid mg Plus Docetaxel

Pharmacokinetic set- all patients in the treated set who were documented to have received at least 1 dose of nintedanib and who had at least 1 valid drug plasma concentration available

Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Treated set- all randomised patients who were documented to have taken at least 1 dose of study medication . Patients were allocated to the treatment groups according to the treatment actually received.

Spots Global Cancer Trial Database for bibf 1120 plus docetaxel