Clinical trial NCT01345682: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Neoplasms
Carcinoma, Squamous Cell
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-05-02
Enrollment: 483
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Central Independent Review
timeFrame: From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death or study completion date (06Dec2016); Up to 60 months
measure: Objective Response (OR)
timeFrame: 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
measure: Disease Control (DC)
timeFrame: 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
measure: Tumour Shrinkage
timeFrame: 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
measure: Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Status Change in Pain Scale
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Status Change in Swallowing Scale
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Status Change in Global Health Status Scale
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Time to Deterioration in Pain
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Time to Deterioration in Swallowing
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
measure: Time to Deterioration in Global Health Status
timeFrame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Other outcomes:
Locations:
city: Harvey
country: United States
facility: 1200.43.00113 Boehringer Ingelheim Investigational Site
state: Illinois
city: Peoria
country: United States
facility: 1200.43.00106 Boehringer Ingelheim Investigational Site
state: Illinois
city: Boston
country: United States
facility: 1200.43.00110 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Omaha
country: United States
facility: 1200.43.00107 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Stony Brook
country: United States
facility: 1200.43.00105 Boehringer Ingelheim Investigational Site
state: New York
city: Philadelphia
country: United States
facility: 1200.43.00102 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: 1200.43.00103 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: San Antonio
country: United States
facility: 1200.43.00109 Boehringer Ingelheim Investigational Site
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: 1200.43.05401 Boehringer Ingelheim Investigational Site
city: Santa Fe
country: Argentina
facility: 1200.43.05402 Boehringer Ingelheim Investigational Site
city: Villa Dominico
country: Argentina
facility: 1200.43.05403 Boehringer Ingelheim Investigational Site
city: Leoben
country: Austria
facility: 1200.43.04303 Boehringer Ingelheim Investigational Site
city: Salzburg
country: Austria
facility: 1200.43.04305 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1200.43.04301 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1200.43.03202 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1200.43.03203 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1200.43.03204 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1200.43.03201 Boehringer Ingelheim Investigational Site
city: Barretos
country: Brazil
facility: 1200.43.05504 Boehringer Ingelheim Investigational Site
city: Jau
country: Brazil
facility: 1200.43.05505 Boehringer Ingelheim Investigational Site
city: Passo Fundo
country: Brazil
facility: 1200.43.05507 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1200.43.05503 Boehringer Ingelheim Investigational Site
city: Rio de Janeiro
country: Brazil
facility: 1200.43.05502 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 1200.43.05501 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 1200.43.05506 Boehringer Ingelheim Investigational Site
city: Olomouc
country: Czechia
facility: 1200.43.04202 Boehringer Ingelheim Investigational Site
city: Prague 2
country: Czechia
facility: 1200.43.04203 Boehringer Ingelheim Investigational Site
city: Prague 8
country: Czechia
facility: 1200.43.04201 Boehringer Ingelheim Investigational Site
city: København Ø
country: Denmark
facility: 1200.43.04501 Boehringer Ingelheim Investigational Site
city: Avignon Cedex 9
country: France
facility: 1200.43.03304 Boehringer Ingelheim Investigational Site
city: Clermont-Ferrand cedex 1
country: France
facility: 1200.43.03306 Boehringer Ingelheim Investigational Site
city: Dijon Cedex
country: France
facility: 1200.43.03312 Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 1200.43.03303 Boehringer Ingelheim Investigational Site
city: Lyon Cedex
country: France
facility: 1200.43.03301 Boehringer Ingelheim Investigational Site
city: Montpellier cedex 5
country: France
facility: 1200.43.03302 Boehringer Ingelheim Investigational Site
city: Nice cedex 2
country: France
facility: 1200.43.03307 Boehringer Ingelheim Investigational Site
city: Paris Cedex 05
country: France
facility: 1200.43.03314 Boehringer Ingelheim Investigational Site
city: Poitiers
country: France
facility: 1200.43.03305 Boehringer Ingelheim Investigational Site
city: Rouen Cedex 1
country: France
facility: 1200.43.03316 Boehringer Ingelheim Investigational Site
city: Saint Herblain Cedex
country: France
facility: 1200.43.03309 Boehringer Ingelheim Investigational Site
city: Vandoeuvre les Nancy cedex
country: France
facility: 1200.43.03310 Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1200.43.03317 Boehringer Ingelheim Investigational Site
city: Aachen
country: Germany
facility: 1200.43.04903 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1200.43.04902 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1200.43.04909 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1200.43.04901 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1200.43.04905 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1200.43.04906 Boehringer Ingelheim Investigational Site
city: Jena
country: Germany
facility: 1200.43.04908 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1200.43.04904 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1200.43.04907 Boehringer Ingelheim Investigational Site
city: Haidari
country: Greece
facility: 1200.43.03004 Boehringer Ingelheim Investigational Site
city: Heraklion
country: Greece
facility: 1200.43.03005 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1200.43.03002 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 1200.43.97201 Boehringer Ingelheim Investigational Site
city: Petach Tikva
country: Israel
facility: 1200.43.97203 Boehringer Ingelheim Investigational Site
city: Tel Hashomer
country: Israel
facility: 1200.43.97204 Boehringer Ingelheim Investigational Site
city: Aosta
country: Italy
facility: 1200.43.03909 Boehringer Ingelheim Investigational Site
city: Cagliari
country: Italy
facility: 1200.43.03908 Boehringer Ingelheim Investigational Site
city: Confreria (CN)
country: Italy
facility: 1200.43.03901 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1200.43.03907 Boehringer Ingelheim Investigational Site
city: Napoli
country: Italy
facility: 1200.43.03903 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1200.43.03905 Boehringer Ingelheim Investigational Site
city: Savona
country: Italy
facility: 1200.43.03902 Boehringer Ingelheim Investigational Site
city: Taormina (ME)
country: Italy
facility: 1200.43.03904 Boehringer Ingelheim Investigational Site
city: Venezia
country: Italy
facility: 1200.43.03906 Boehringer Ingelheim Investigational Site
city: Viterbo
country: Italy
facility: 1200.43.03910 Boehringer Ingelheim Investigational Site
city: Aichi, Nagoya
country: Japan
facility: 1200.43.08106 Boehringer Ingelheim Investigational Site
city: Chiba, Kashiwa
country: Japan
facility: 1200.43.08103 Boehringer Ingelheim Investigational Site
city: Ehime, Matsuyama
country: Japan
facility: 1200.43.08108 Boehringer Ingelheim Investigational Site
city: Hyogo, Akashi
country: Japan
facility: 1200.43.08111 Boehringer Ingelheim Investigational Site
city: Hyogo, Kobe
country: Japan
facility: 1200.43.08107 Boehringer Ingelheim Investigational Site
city: Kanagawa, Isehara
country: Japan
facility: 1200.43.08109 Boehringer Ingelheim Investigational Site
city: Miyagi, Natori
country: Japan
facility: 1200.43.08114 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1200.43.08110 Boehringer Ingelheim Investigational Site
city: Shizuoka, Sunto-gun
country: Japan
facility: 1200.43.08105 Boehringer Ingelheim Investigational Site
city: Tochigi, Shimotsuke
country: Japan
facility: 1200.43.08102 Boehringer Ingelheim Investigational Site
city: Tokyo, Koto-ku
country: Japan
facility: 1200.43.08113 Boehringer Ingelheim Investigational Site
city: Tokyo, Meguro-ku
country: Japan
facility: 1200.43.08104 Boehringer Ingelheim Investigational Site
city: Tokyo, Minato-ku
country: Japan
facility: 1200.43.08112 Boehringer Ingelheim Investigational Site
city: Mexico
country: Mexico
facility: 1200.43.05202 Boehringer Ingelheim Investigational Site
city: Ivanovo
country: Russian Federation
facility: 1200.43.00704 Boehringer Ingelheim Investigational Site
city: Kurski
country: Russian Federation
facility: 1200.43.00706 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1200.43.00709 Boehringer Ingelheim Investigational Site
city: Omsk
country: Russian Federation
facility: 1200.43.00703 Boehringer Ingelheim Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: 1200.43.00710 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1200.43.00707 Boehringer Ingelheim Investigational Site
city: Ufa
country: Russian Federation
facility: 1200.43.00705 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1200.43.02703 Boehringer Ingelheim Investigational Site
city: Kraaifontein, Cape Town
country: South Africa
facility: 1200.43.02704 Boehringer Ingelheim Investigational Site
city: Parktown, Johannesburg
country: South Africa
facility: 1200.43.02701 Boehringer Ingelheim Investigational Site
city: Pretoria
country: South Africa
facility: 1200.43.02702 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.43.03401 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.43.03404 Boehringer Ingelheim Investigational Site
city: Girona
country: Spain
facility: 1200.43.03405 Boehringer Ingelheim Investigational Site
city: Málaga
country: Spain
facility: 1200.43.03406 Boehringer Ingelheim Investigational Site
city: Salamanca
country: Spain
facility: 1200.43.03402 Boehringer Ingelheim Investigational Site
city: Zaragoza
country: Spain
facility: 1200.43.03403 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1200.43.04602 Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: 1200.43.04101 Boehringer Ingelheim Investigational Site
city: Bern
country: Switzerland
facility: 1200.43.04102 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Cohen EEW, Licitra LF, Burtness B, Fayette J, Gauler T, Clement PM, Grau JJ, Del Campo JM, Mailliez A, Haddad RI, Vermorken JB, Tahara M, Guigay J, Geoffrois L, Merlano MC, Dupuis N, Kramer N, Cong XJ, Gibson N, Solca F, Ehrnrooth E, Machiels JH. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer. Ann Oncol. 2017 Oct 1;28(10):2526-2532. doi: 10.1093/annonc/mdx344.
citation: Clement PM, Gauler T, Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Cohen EE, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Vermorken JB; LUX-H&N 1 investigators. Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial. Ann Oncol. 2016 Aug;27(8):1585-93. doi: 10.1093/annonc/mdw151. Epub 2016 Apr 15.
citation: Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):583-94. doi: 10.1016/S1470-2045(15)70124-5. Epub 2015 Apr 16.