LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy

Phase 3

Completed

Conditions: Head and Neck Neoplasms
Carcinoma, Squamous Cell

Interventions: Drug: Methotrexate
Drug: Afatinib

Registration Number: NCT01345682

Lead Sponsor: Boehringer Ingelheim

Brief Summary: This randomised, open-label, phase III study will be performed in patients with R/M head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy. The objectives of the trial are to compare the efficacy and safety of afatinib versus methotrexate

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 483

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methotrexate	Methotrexate	Weekly
Afatinib (BIBW 2992)	Afatinib	Once daily

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Based on Central Independent Review	From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months	PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016). The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied: * At least 20% increase in the Sum of Diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm * Appearance of one or more new lesions * Unequivocal progression of existing non-target lesions

Secondary Outcome Measures

Name	Time	Method
Tumour Shrinkage	Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months	Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis. Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase. Percentage of Participants with Tumour shrinkage as per the categories (\>=20% increase, \>=0 - \<20% increase, \>0 - \<30% decrease, \>=30 - \<50% decrease, \>=50% decrease) are presented.
Overall Survival (OS)	From randomization until death or study completion date (06Dec2016); Up to 60 months	Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive.
Time to Deterioration in Global Health Status	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The time to deterioration was defined as the time from randomisation to a score decreased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Objective Response (OR)	Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months	OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-Progressive Disease (PD) in NTL leads to PR * CR in TL, but not evaluated NTL leads to PR * PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; All the above scenarios should also satisfy 'No occurrence of new lesions'.
Disease Control (DC)	Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months	DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-PD in NTL leads to PR * CR in TL, but not evaluated NTL leads to PR * PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; SD for TL: change in the sum of diameters does not satisfy PR or PD. SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions.
Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date.
Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date.
Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date.
Status Change in Pain Scale	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Status Change in Swallowing Scale	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Status Change in Global Health Status Scale	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Time to Deterioration in Pain	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time to Deterioration in Swallowing	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.	The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Trial Locations

Locations (101): 1200.43.08111 Boehringer Ingelheim Investigational Site
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Hyogo, Akashi, Japan
1200.43.08107 Boehringer Ingelheim Investigational Site
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Hyogo, Kobe, Japan
1200.43.03303 Boehringer Ingelheim Investigational Site
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Lille Cedex, France
1200.43.05403 Boehringer Ingelheim Investigational Site
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Villa Dominico, Argentina
1200.43.05505 Boehringer Ingelheim Investigational Site
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Jau, Brazil
1200.43.03302 Boehringer Ingelheim Investigational Site
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Montpellier cedex 5, France
1200.43.04303 Boehringer Ingelheim Investigational Site
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Leoben, Austria
1200.43.03907 Boehringer Ingelheim Investigational Site
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Milano, Italy
1200.43.03202 Boehringer Ingelheim Investigational Site
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Bruxelles, Belgium
1200.43.05507 Boehringer Ingelheim Investigational Site
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Passo Fundo, Brazil
1200.43.03301 Boehringer Ingelheim Investigational Site
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Lyon Cedex, France
1200.43.04203 Boehringer Ingelheim Investigational Site
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Prague 2, Czechia
1200.43.03307 Boehringer Ingelheim Investigational Site
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Nice cedex 2, France
1200.43.97201 Boehringer Ingelheim Investigational Site
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Haifa, Israel
1200.43.04201 Boehringer Ingelheim Investigational Site
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Prague 8, Czechia
1200.43.04902 Boehringer Ingelheim Investigational Site
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Berlin, Germany
1200.43.03909 Boehringer Ingelheim Investigational Site
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Aosta, Italy
1200.43.03312 Boehringer Ingelheim Investigational Site
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Dijon Cedex, France
1200.43.05503 Boehringer Ingelheim Investigational Site
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Porto Alegre, Brazil
1200.43.00107 Boehringer Ingelheim Investigational Site
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Omaha, Nebraska, United States
1200.43.05402 Boehringer Ingelheim Investigational Site
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Santa Fe, Argentina
1200.43.04906 Boehringer Ingelheim Investigational Site
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Hannover, Germany
1200.43.03901 Boehringer Ingelheim Investigational Site
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Confreria (CN), Italy
1200.43.03905 Boehringer Ingelheim Investigational Site
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Palermo, Italy
1200.43.03314 Boehringer Ingelheim Investigational Site
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Paris Cedex 05, France
1200.43.03304 Boehringer Ingelheim Investigational Site
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Avignon Cedex 9, France
1200.43.08106 Boehringer Ingelheim Investigational Site
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Aichi, Nagoya, Japan
1200.43.04908 Boehringer Ingelheim Investigational Site
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Jena, Germany
1200.43.05504 Boehringer Ingelheim Investigational Site
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Barretos, Brazil
1200.43.04904 Boehringer Ingelheim Investigational Site
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Leipzig, Germany
1200.43.04909 Boehringer Ingelheim Investigational Site
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Dresden, Germany
1200.43.03316 Boehringer Ingelheim Investigational Site
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Rouen Cedex 1, France
1200.43.03004 Boehringer Ingelheim Investigational Site
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Haidari, Greece
1200.43.03404 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1200.43.03902 Boehringer Ingelheim Investigational Site
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Savona, Italy
1200.43.08110 Boehringer Ingelheim Investigational Site
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Osaka, Osaka, Japan
1200.43.03403 Boehringer Ingelheim Investigational Site
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Zaragoza, Spain
1200.43.03310 Boehringer Ingelheim Investigational Site
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Vandoeuvre les Nancy cedex, France
1200.43.00704 Boehringer Ingelheim Investigational Site
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Ivanovo, Russian Federation
1200.43.04903 Boehringer Ingelheim Investigational Site
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Aachen, Germany
1200.43.08102 Boehringer Ingelheim Investigational Site
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Tochigi, Shimotsuke, Japan
1200.43.08113 Boehringer Ingelheim Investigational Site
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Tokyo, Koto-ku, Japan
1200.43.08112 Boehringer Ingelheim Investigational Site
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Tokyo, Minato-ku, Japan
1200.43.03406 Boehringer Ingelheim Investigational Site
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Málaga, Spain
1200.43.02704 Boehringer Ingelheim Investigational Site
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Kraaifontein, Cape Town, South Africa
1200.43.97203 Boehringer Ingelheim Investigational Site
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Petach Tikva, Israel
1200.43.03402 Boehringer Ingelheim Investigational Site
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Salamanca, Spain
1200.43.00710 Boehringer Ingelheim Investigational Site
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Pyatigorsk, Russian Federation
1200.43.02703 Boehringer Ingelheim Investigational Site
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Cape Town, South Africa
1200.43.03401 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1200.43.02702 Boehringer Ingelheim Investigational Site
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Pretoria, South Africa
1200.43.00110 Boehringer Ingelheim Investigational Site
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Boston, Massachusetts, United States
1200.43.00103 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1200.43.00105 Boehringer Ingelheim Investigational Site
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Stony Brook, New York, United States
1200.43.04501 Boehringer Ingelheim Investigational Site
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København Ø, Denmark
1200.43.04602 Boehringer Ingelheim Investigational Site
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Göteborg, Sweden
1200.43.03908 Boehringer Ingelheim Investigational Site
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Cagliari, Italy
1200.43.03903 Boehringer Ingelheim Investigational Site
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Napoli, Italy
1200.43.03904 Boehringer Ingelheim Investigational Site
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Taormina (ME), Italy
1200.43.03910 Boehringer Ingelheim Investigational Site
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Viterbo, Italy
1200.43.04305 Boehringer Ingelheim Investigational Site
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Salzburg, Austria
1200.43.03005 Boehringer Ingelheim Investigational Site
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Heraklion, Greece
1200.43.04102 Boehringer Ingelheim Investigational Site
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Bern, Switzerland
1200.43.03002 Boehringer Ingelheim Investigational Site
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Thessaloniki, Greece
1200.43.05202 Boehringer Ingelheim Investigational Site
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Mexico, Mexico
1200.43.05506 Boehringer Ingelheim Investigational Site
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Sao Paulo, Brazil
1200.43.08108 Boehringer Ingelheim Investigational Site
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Ehime, Matsuyama, Japan
1200.43.08109 Boehringer Ingelheim Investigational Site
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Kanagawa, Isehara, Japan
1200.43.08104 Boehringer Ingelheim Investigational Site
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Tokyo, Meguro-ku, Japan
1200.43.08114 Boehringer Ingelheim Investigational Site
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Miyagi, Natori, Japan
1200.43.08105 Boehringer Ingelheim Investigational Site
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Shizuoka, Sunto-gun, Japan
1200.43.03305 Boehringer Ingelheim Investigational Site
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Poitiers, France
1200.43.03309 Boehringer Ingelheim Investigational Site
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Saint Herblain Cedex, France
1200.43.03317 Boehringer Ingelheim Investigational Site
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Villejuif Cedex, France
1200.43.04907 Boehringer Ingelheim Investigational Site
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Mannheim, Germany
1200.43.00113 Boehringer Ingelheim Investigational Site
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Harvey, Illinois, United States
1200.43.00106 Boehringer Ingelheim Investigational Site
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Peoria, Illinois, United States
1200.43.00102 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1200.43.00109 Boehringer Ingelheim Investigational Site
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San Antonio, Texas, United States
1200.43.05401 Boehringer Ingelheim Investigational Site
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Ciudad Autonoma de Bs As, Argentina
1200.43.04301 Boehringer Ingelheim Investigational Site
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Wien, Austria
1200.43.03203 Boehringer Ingelheim Investigational Site
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Edegem, Belgium
1200.43.03204 Boehringer Ingelheim Investigational Site
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Gent, Belgium
1200.43.05501 Boehringer Ingelheim Investigational Site
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Sao Paulo, Brazil
1200.43.04202 Boehringer Ingelheim Investigational Site
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Olomouc, Czechia
1200.43.03306 Boehringer Ingelheim Investigational Site
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Clermont-Ferrand cedex 1, France
1200.43.04905 Boehringer Ingelheim Investigational Site
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Hamburg, Germany
1200.43.97204 Boehringer Ingelheim Investigational Site
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Tel Hashomer, Israel
1200.43.03906 Boehringer Ingelheim Investigational Site
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Venezia, Italy
1200.43.08103 Boehringer Ingelheim Investigational Site
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Chiba, Kashiwa, Japan
1200.43.00703 Boehringer Ingelheim Investigational Site
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Omsk, Russian Federation
1200.43.00706 Boehringer Ingelheim Investigational Site
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Kurski, Russian Federation
1200.43.03405 Boehringer Ingelheim Investigational Site
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Girona, Spain
1200.43.00709 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
1200.43.00707 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
1200.43.02701 Boehringer Ingelheim Investigational Site
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Parktown, Johannesburg, South Africa
1200.43.00705 Boehringer Ingelheim Investigational Site
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Ufa, Russian Federation
1200.43.04101 Boehringer Ingelheim Investigational Site
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Basel, Switzerland
1200.43.05502 Boehringer Ingelheim Investigational Site
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Rio de Janeiro, Brazil
1200.43.04901 Boehringer Ingelheim Investigational Site
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Essen, Germany
1200.43.03201 Boehringer Ingelheim Investigational Site
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Leuven, Belgium