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

Phase 3

Completed

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: placebo plus docetaxel
Drug: BIBF 1120 plus docetaxel

Registration Number: NCT00805194

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1314

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo plus docetaxel	placebo plus docetaxel	Placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel
BIBF 1120 plus docetaxel	BIBF 1120 plus docetaxel	BIBF 1120 2 times daily along with standard therapy of docetaxel

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) as Assessed by Central Independent Review	From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Confirmed Objective Tumour Response	From randomisation until cut-off date 15 February 2013	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 Tumour Response	From randomisation until cut-off date 15 February 2013	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	From randomisation until cut-off date 15 February 2013	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.
Quality of Life (QoL)	From randomisation until cut-off date 15 February 2013	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
Duration of Disease Control	From randomisation until cut-off date 15 February 2013	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.
Clinical Improvement	From randomisation until cut-off date 15 February 2013	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.
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide	Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3	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.
Overall Survival (Key Secondary Endpoint)	From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )	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 of Progression Free Survival (PFS) as Assessed by Central Independent Review	From randomisation until cut-off date 15 February 2013	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 of Progression Free Survival (PFS) as Assessed by Investigator	From randomisation until cut-off date 15 February 2013	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.
Objective Tumour Response	From randomisation until cut-off date 15 February 2013	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.
Change From Baseline in Tumour Size	From randomisation until cut-off date 15 February 2013	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.
Incidence and Intensity of Adverse Events	From the first drug administration until 28 days after the last drug administration, up to 42 months	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.

Trial Locations

Locations (208): LKH-Univ. Hospital Graz
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Graz, Austria
KH St. Vinzenz, Zams, Int. Abtlg.
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Kufstein, Austria
AKH d. Stadt Linz, Pulmologie
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Linz, Austria
Bobruisk Inter-distict
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Bobruisk, Belarus
Brest Regional Clinical
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Brest Region, Belarus
Gomel Regional Clinical
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Gomel, Belarus
Scientific Research Minsk
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Minsk Region, Belarus
Public Health Inst. Minsk City Clinical Oncology Dispensary
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Minsk, Belarus
Mogilov Regional Oncological Dispensary
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Mogilov, Belarus
Vitebsk Regional Clinical Oncology Dispensary
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Vitebsk, Belarus
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LKH-Univ. Hospital Graz
🇦🇹Graz, Austria