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

Head and Neck Neoplasms Clinical Trial

Official title:

A Randomised, Open-label, Phase III Study to Evaluate the Efficacy and Safety of Oral Afatinib (BIBW 2992) Versus Intravenous Methotrexate in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Who Have Progressed After Platinum-based Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01345682
• Other study ID #: 1200.43
• Secondary ID: 2011-000391-34
• Status: Completed
• Phase: Phase 3
• First received: April 28, 2011
• Last updated: January 19, 2018
• Start date: January 5, 2012
• Est. completion date: December 6, 2016

Study information

• Verified date: January 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 483
• Est. completion date: December 6, 2016
• Est. primary completion date: March 15, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Histologically or cytologically confirmed R/M HNSCC of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy

2. Documented progressive disease based on investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) following receipt of at least two cycles of cisplatin or carboplatin administered for R/M disease

3. Measurable disease according to RECIST

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion criteria:

1. Progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC

2. Any other than one previous platinum based systemic regimen given for R/M disease

3. Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules

4. Pregnancy or breast feeding

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms

Intervention

Drug:
• Afatinib
Once daily
• Methotrexate
Weekly

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Czechia,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Mexico,  Russian Federation,  South Africa,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Based on Central Independent Review	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	From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months
Secondary	Overall Survival (OS)	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.	From randomization until death or study completion date (06Dec2016); Up to 60 months
Secondary	Objective Response (OR)	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'.	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
Secondary	Disease Control (DC)	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.	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
Secondary	Tumour Shrinkage	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.	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
Secondary	Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Status Change in Pain Scale	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Status Change in Swallowing Scale	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Status Change in Global Health Status Scale	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Time to Deterioration in Pain	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Time to Deterioration in Swallowing	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Secondary	Time to Deterioration in Global Health Status	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.	From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

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