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

NCT01345682 | Completed Phase 3 Results

• 2 other identifiers: 1200.432011-000391-34
• Study Type: interventional
• Target: 483
• Locations: 19 countries
• Sites: 101

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

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Overall Survival (OS)

  From randomization until death or study completion date (06Dec2016); Up to 60 months

• 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

• 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

• 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

• 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.

Study Arms (2)

Afatinib (BIBW 2992)

EXPERIMENTAL

Once daily

Drug: Afatinib

Methotrexate

ACTIVE COMPARATOR

Weekly

Drug: Methotrexate

Interventions

Afatinib DRUG

Once daily

Afatinib (BIBW 2992)

Methotrexate DRUG

Weekly

Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed R/M HNSCC of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy
• 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
• Measurable disease according to RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

You may not qualify if:

• Progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC
• Any other than one previous platinum based systemic regimen given for R/M disease
• Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules
• Pregnancy or breast feeding

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (101)

1200.43.00113 Boehringer Ingelheim Investigational Site

Harvey, Illinois, United States

Location

1200.43.00106 Boehringer Ingelheim Investigational Site

Peoria, Illinois, United States

Location

1200.43.00110 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Location

1200.43.00107 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

Location

1200.43.00105 Boehringer Ingelheim Investigational Site

Stony Brook, New York, United States

Location

1200.43.00102 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1200.43.00103 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1200.43.00109 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

Location

1200.43.05401 Boehringer Ingelheim Investigational Site

Ciudad Autonoma de Bs As, Argentina

Location

1200.43.05402 Boehringer Ingelheim Investigational Site

Santa Fe, Argentina

Location

1200.43.05403 Boehringer Ingelheim Investigational Site

Villa Domínico, Argentina

Location

1200.43.04303 Boehringer Ingelheim Investigational Site

Leoben, Austria

Location

1200.43.04305 Boehringer Ingelheim Investigational Site

Salzburg, Austria

Location

1200.43.04301 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1200.43.03202 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1200.43.03203 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

1200.43.03204 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

1200.43.03201 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

1200.43.05504 Boehringer Ingelheim Investigational Site

Barretos, Brazil

Location

1200.43.05505 Boehringer Ingelheim Investigational Site

Jaú, Brazil

Location

1200.43.05507 Boehringer Ingelheim Investigational Site

Passo Fundo, Brazil

Location

1200.43.05503 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

1200.43.05502 Boehringer Ingelheim Investigational Site

Rio de Janeiro, Brazil

Location

1200.43.05501 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

1200.43.05506 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

1200.43.04202 Boehringer Ingelheim Investigational Site

Olomouc, Czechia

Location

1200.43.04201 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1200.43.04203 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1200.43.04501 Boehringer Ingelheim Investigational Site

København Ø, Denmark

Location

1200.43.03304 Boehringer Ingelheim Investigational Site

Avignon, France

Location

1200.43.03306 Boehringer Ingelheim Investigational Site

Clermont-Ferrand, 63011, France

Location

1200.43.03312 Boehringer Ingelheim Investigational Site

Dijon, France

Location

1200.43.03303 Boehringer Ingelheim Investigational Site

Lille, France

Location

1200.43.03301 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1200.43.03302 Boehringer Ingelheim Investigational Site

Montpellier, France

Location

1200.43.03307 Boehringer Ingelheim Investigational Site

Nice, France

Location

1200.43.03314 Boehringer Ingelheim Investigational Site

Paris, France

Location

1200.43.03305 Boehringer Ingelheim Investigational Site

Poitiers, France

Location

1200.43.03316 Boehringer Ingelheim Investigational Site

Rouen, France

Location

1200.43.03309 Boehringer Ingelheim Investigational Site

Saint-Herblain, France

Location

1200.43.03310 Boehringer Ingelheim Investigational Site

Vandœuvre-lès-Nancy, France

Location

1200.43.03317 Boehringer Ingelheim Investigational Site

Villejuif, France

Location

1200.43.04903 Boehringer Ingelheim Investigational Site

Aachen, Germany

Location

1200.43.04902 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1200.43.04909 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1200.43.04901 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1200.43.04905 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1200.43.04906 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1200.43.04908 Boehringer Ingelheim Investigational Site

Jena, Germany

Location

1200.43.04904 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1200.43.04907 Boehringer Ingelheim Investigational Site

Mannheim, Germany

Location

1200.43.03004 Boehringer Ingelheim Investigational Site

Haidari, Greece

Location

1200.43.03005 Boehringer Ingelheim Investigational Site

Heraklion, Greece

Location

1200.43.03002 Boehringer Ingelheim Investigational Site

Thessaloniki, Greece

Location

1200.43.97201 Boehringer Ingelheim Investigational Site

Haifa, Israel

Location

1200.43.97203 Boehringer Ingelheim Investigational Site

Petah Tikva, Israel

Location

1200.43.97204 Boehringer Ingelheim Investigational Site

Tel Litwinsky, Israel

Location

1200.43.03909 Boehringer Ingelheim Investigational Site

Aosta, Italy

Location

1200.43.03908 Boehringer Ingelheim Investigational Site

Cagliari, Italy

Location

1200.43.03901 Boehringer Ingelheim Investigational Site

Confreria (CN), Italy

Location

1200.43.03907 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1200.43.03903 Boehringer Ingelheim Investigational Site

Napoli, Italy

Location

1200.43.03905 Boehringer Ingelheim Investigational Site

Palermo, Italy

Location

1200.43.03902 Boehringer Ingelheim Investigational Site

Savona, Italy

Location

1200.43.03904 Boehringer Ingelheim Investigational Site

Taormina (ME), Italy

Location

1200.43.03906 Boehringer Ingelheim Investigational Site

Venezia, Italy

Location

1200.43.03910 Boehringer Ingelheim Investigational Site

Viterbo, Italy

Location

1200.43.08106 Boehringer Ingelheim Investigational Site

Aichi, Nagoya, Japan

Location

1200.43.08103 Boehringer Ingelheim Investigational Site

Chiba, Kashiwa, Japan

Location

1200.43.08108 Boehringer Ingelheim Investigational Site

Ehime, Matsuyama, Japan

Location

1200.43.08111 Boehringer Ingelheim Investigational Site

Hyogo, Akashi, Japan

Location

1200.43.08107 Boehringer Ingelheim Investigational Site

Hyogo, Kobe, Japan

Location

1200.43.08109 Boehringer Ingelheim Investigational Site

Kanagawa, Isehara, Japan

Location

1200.43.08114 Boehringer Ingelheim Investigational Site

Miyagi, Natori, Japan

Location

1200.43.08110 Boehringer Ingelheim Investigational Site

Osaka, Osaka, Japan

Location

1200.43.08105 Boehringer Ingelheim Investigational Site

Shizuoka, Sunto-gun, Japan

Location

1200.43.08102 Boehringer Ingelheim Investigational Site

Tochigi, Shimotsuke, Japan

Location

1200.43.08113 Boehringer Ingelheim Investigational Site

Tokyo, Koto-ku, Japan

Location

1200.43.08104 Boehringer Ingelheim Investigational Site

Tokyo, Meguro-ku, Japan

Location

1200.43.08112 Boehringer Ingelheim Investigational Site

Tokyo, Minato-ku, Japan

Location

1200.43.05202 Boehringer Ingelheim Investigational Site

México, Mexico

Location

1200.43.00704 Boehringer Ingelheim Investigational Site

Ivanovo, Russia

Location

1200.43.00706 Boehringer Ingelheim Investigational Site

Kurski, Russia

Location

1200.43.00709 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

1200.43.00703 Boehringer Ingelheim Investigational Site

Omsk, Russia

Location

1200.43.00710 Boehringer Ingelheim Investigational Site

Pyatigorsk, Russia

Location

1200.43.00707 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1200.43.00705 Boehringer Ingelheim Investigational Site

Ufa, Russia

Location

1200.43.02703 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1200.43.02704 Boehringer Ingelheim Investigational Site

Kraaifontein, Cape Town, South Africa

Location

1200.43.02701 Boehringer Ingelheim Investigational Site

Parktown, Johannesburg, South Africa

Location

1200.43.02702 Boehringer Ingelheim Investigational Site

Pretoria, South Africa

Location

1200.43.03401 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.43.03404 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.43.03405 Boehringer Ingelheim Investigational Site

Girona, Spain

Location

1200.43.03406 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1200.43.03402 Boehringer Ingelheim Investigational Site

Salamanca, Spain

Location

1200.43.03403 Boehringer Ingelheim Investigational Site

Zaragoza, Spain

Location

1200.43.04602 Boehringer Ingelheim Investigational Site

Gothenburg, Sweden

Location

1200.43.04101 Boehringer Ingelheim Investigational Site

Basel, 4031, Switzerland

Location

1200.43.04102 Boehringer Ingelheim Investigational Site

Bern, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 28961833 DERIVED

• 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.

  PMID: 27084954 DERIVED

• 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.

  PMID: 25892145 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Afatinib; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2011
• First Posted: May 2, 2011
• Study Start: January 5, 2012
• Primary Completion: March 15, 2014
• Study Completion: December 6, 2016
• Last Updated: February 15, 2018
• Results First Posted: April 14, 2015

Record last verified: 2018-01

Locations

ME (1); SE (1); GR (3); BE (4); IT (10); IL (3); ES (6); US (8); BR (7); DE (9); DK (1); AR (3); JP (13); RU (7); ZA (4); CZ (3); AU (3); FR (13); CH (2)