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NCT00805194

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

Completed Phase 3 Results posted Last updated 5 December 2018
What this trial tests

Phase 3 trial testing placebo plus docetaxel in Carcinoma, Non-Small-Cell Lung in 1,314 participants. Completed in 13 November 2017.

Timeline
3 December 2008
Primary endpoint
2 November 2010
13 November 2017

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment1,314
Start date3 December 2008
Primary completion2 November 2010
Estimated completion13 November 2017
Sites210 locations across Italy, Poland, South Korea, Croatia, Denmark, Russia, Belgium, Lithuania

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Nintedanib Plus Docetaxel3.41.5 – 5.7
Placebo Plus Docetaxel2.71.4 – 4.6
Overall Survival (Key Secondary Endpoint) Secondary · 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)

Adenocarcinoma and <9 months
GroupValue95% CI
Nintedanib Plus Docetaxel10.95.1 – 21.9
Placebo Plus Docetaxel7.94.5 – 14.5
Adenocarcinoma
GroupValue95% CI
Nintedanib Plus Docetaxel12.65.5 – 24.2
Placebo Plus Docetaxel10.35.5 – 19.9
All patients
GroupValue95% CI
Nintedanib Plus Docetaxel10.15.0 – 19.4
Placebo Plus Docetaxel9.14.8 – 17.2
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review Secondary · 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.

GroupValue95% CI
Nintedanib Plus Docetaxel3.51.5 – 5.7
Placebo Plus Docetaxel2.71.4 – 5.5
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator Secondary · 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.

GroupValue95% CI
Nintedanib Plus Docetaxel4.22.1 – 7.1
Placebo Plus Docetaxel3.01.4 – 5.7
Objective Tumour Response Secondary · 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.

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel4.4
Placebo Plus Docetaxel3.3
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel10.4
Placebo Plus Docetaxel7.6
Duration of Confirmed Objective Tumour Response Secondary · 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.

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel4.33.0 – 5.7
Placebo Plus Docetaxel4.32.8 – 8.5
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel5.74.1 – 10.0
Placebo Plus Docetaxel5.53.9 – 9.6
Time to Confirmed Objective Tumour Response Secondary · 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.

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel1.51.4 – 3.0
Placebo Plus Docetaxel2.91.4 – 5.6
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel2.61.4 – 4.0
Placebo Plus Docetaxel2.71.4 – 4.1
Disease Control Secondary · 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

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel54.0
Placebo Plus Docetaxel41.3
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel63.4
Placebo Plus Docetaxel51.4
Duration of Disease Control Secondary · 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.

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel5.64.1 – 7.1
Placebo Plus Docetaxel5.64.0 – 8.2
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel5.74.2 – 8.4
Placebo Plus Docetaxel5.64.1 – 8.5
Change From Baseline in Tumour Size Secondary · 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.

central independent reviewer
GroupValue95% CI
Nintedanib Plus Docetaxel-4.87-6.62 – -3.12
Placebo Plus Docetaxel0.58-1.19 – 2.35
investigator assessment
GroupValue95% CI
Nintedanib Plus Docetaxel-10.34-12.58 – -8.11
Placebo Plus Docetaxel-2.14-4.39 – 0.10
Clinical Improvement Secondary · 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.

GroupValue95% CI
Nitedanib Plus Docetaxel5.92.1 – 22.7
Placebo Plus Docetaxel5.22.1 – 19.2
Quality of Life (QoL) Secondary · 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 (QL

Time to deterioration of cough
GroupValue95% CI
Nitedanib Plus Docetaxel4.31.6 – 11.8
Placebo Plus Docetaxel3.51.5 – 12.6
Time to deterioration of dyspnoea
GroupValue95% CI
Nitedanib Plus Docetaxel2.00.8 – 4.2
Placebo Plus Docetaxel2.10.8 – 4.5
Time to deterioration of pain
GroupValue95% CI
Nitedanib Plus Docetaxel2.81.1 – 6.5
Placebo Plus Docetaxel2.60.8 – 5.8

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first drug administration until 28 days after the last drug administration, up to 42 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nintedanib Plus Docetaxel
Serious: 224/652 (34%)
Deaths: 107/652
Placebo Plus Docetaxel
Serious: 206/655 (31%)
Deaths: 77/655

Serious adverse events (232 terms)

ReactionSystemNintedanib Plus DocetaxelPlacebo Plus Docetaxel
Febrile neutropeniaBlood and lymphatic system disorders——
DyspnoeaRespiratory, thoracic and mediastinal disorders——
PneumoniaInfections and infestations——
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)——
NeutropeniaBlood and lymphatic system disorders——
DiarrhoeaGastrointestinal disorders——
General physical health deteriorationGeneral disorders——
PyrexiaGeneral disorders——
VomitingGastrointestinal disorders——
Chest painGeneral disorders——
Pleural effusionRespiratory, thoracic and mediastinal disorders——
Respiratory failureRespiratory, thoracic and mediastinal disorders——
AstheniaGeneral disorders——
FatigueGeneral disorders——
SepsisInfections and infestations——
HaemoptysisRespiratory, thoracic and mediastinal disorders——
AnaemiaBlood and lymphatic system disorders——
Neutrophil count decreasedInvestigations——
Pulmonary embolismRespiratory, thoracic and mediastinal disorders——
Atrial fibrillationCardiac disorders——
DehydrationMetabolism and nutrition disorders——
Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders——
Pericardial effusionCardiac disorders——
Abdominal painGastrointestinal disorders——
BronchitisInfections and infestations——
Other adverse events (32 terms — click to expand)

ReactionSystemNintedanib Plus DocetaxelPlacebo Plus Docetaxel
DiarrhoeaGastrointestinal disorders——
Neutrophil count decreasedInvestigations——
FatigueGeneral disorders——
Alanine aminotransferase increasedInvestigations——
NauseaGastrointestinal disorders——
White blood cell count decreasedInvestigations——
Aspartate aminotransferase increasedInvestigations——
Decreased appetiteMetabolism and nutrition disorders——
AlopeciaSkin and subcutaneous tissue disorders——
CoughRespiratory, thoracic and mediastinal disorders——
VomitingGastrointestinal disorders——
DyspnoeaRespiratory, thoracic and mediastinal disorders——
PyrexiaGeneral disorders——
Haemoglobin decreasedInvestigations——
ConstipationGastrointestinal disorders——
NeutropeniaBlood and lymphatic system disorders——
StomatitisGastrointestinal disorders——
AstheniaGeneral disorders——
Chest painGeneral disorders——
Peripheral sensory neuropathyNervous system disorders——
ArthralgiaMusculoskeletal and connective tissue disorders——
MyalgiaMusculoskeletal and connective tissue disorders——
Back painMusculoskeletal and connective tissue disorders——
AnaemiaBlood and lymphatic system disorders——
Oedema peripheralGeneral disorders——
HeadacheNervous system disorders——
Pain in extremityMusculoskeletal and connective tissue disorders——
Blood alkaline phosphatase increasedInvestigations——
InsomniaPsychiatric disorders——
Abdominal painGastrointestinal disorders——
DizzinessNervous system disorders——
DysgeusiaNervous system disorders——

Most-reported serious reactions: Febrile neutropenia, Dyspnoea, Pneumonia, Malignant neoplasm progression, Neutropenia, Diarrhoea, General physical health deterioration, Pyrexia.

Data from ClinicalTrials.gov NCT00805194 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial.
    Reck M, Kaiser R, Mellemgaard A, Douillard JY, et al · · 2014 · cited 721× · PMID 24411639 · DOI 10.1016/s1470-2045(13)70586-2
  2. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis.
    Wollin L, Wex E, Pautsch A, Schnapp G, et al · · 2015 · cited 698× · PMID 25745043 · DOI 10.1183/09031936.00174914
  3. Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy.
    Qin S, Li A, Yi M, Yu S, et al · · 2019 · cited 221× · PMID 30866992 · DOI 10.1186/s13045-019-0718-5
  4. Tumor stroma as targets for cancer therapy.
    Zhang J, Liu J. · · 2013 · cited 139× · PMID 23064233 · DOI 10.1016/j.pharmthera.2012.10.003
  5. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment.
    Liu G, Chen T, Ding Z, Wang Y, et al · · 2021 · cited 131× · PMID 33655556 · DOI 10.1111/cpr.13009
  6. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges.
    Deng GL, Zeng S, Shen H. · · 2015 · cited 115× · PMID 25914779 · DOI 10.4254/wjh.v7.i5.787
  7. Targeting fibroblast growth factor pathways in prostate cancer.
    Corn PG, Wang F, McKeehan WL, Navone N. · · 2013 · cited 87× · PMID 24052019 · DOI 10.1158/1078-0432.ccr-13-1550
  8. BIBF 1120 (nintedanib), a triple angiokinase inhibitor, induces hypoxia but not EMT and blocks progression of preclinical models of lung and pancreatic cancer.
    Kutluk Cenik B, Ostapoff KT, Gerber DE, Brekken RA. · · 2013 · cited 84× · PMID 23729403 · DOI 10.1158/1535-7163.mct-12-0995

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