LUX-Head&Neck 3: Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy
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.
2 other identifiers
interventional
340
8 countries
53
Brief Summary
This randomized, open-label, phase III study will be performed in patients with recurrent and/or metastatic head and neck cancer which has progressed after platinum-based therapy. The objectives of this trial are to compare the efficacy and safety of afatinib versus methotrexate.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2013
Longer than P75 for phase_3
53 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 15, 2013
CompletedFirst Posted
Study publicly available on registry
May 17, 2013
CompletedStudy Start
First participant enrolled
June 7, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 22, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 2, 2024
CompletedResults Posted
Study results publicly available
January 12, 2026
CompletedJanuary 12, 2026
January 1, 2026
5.2 years
May 15, 2013
October 1, 2025
January 7, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
Progression-free survival (PFS) was defined as the time from the date of randomization to the date of disease progression (PD) evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1). or to the date of death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier curves generated for each group.
From randomization until disease progression, death, or primary completion date, whichever occurs first. Up to 35 months.
Secondary Outcomes (12)
Objective Response (OR)
From randomization until earliest of disease progression, death, or interim cut-off date (11-Apr-2019). Up to 35 months.
Overall Survival (OS)
From randomization until death. Up to 6 years.
Time to Deterioration in Global Health Status
From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 30 months.
Time to Deterioration in Pain Symptoms
From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 19 months.
Time to Deterioration in Swallowing
From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 19 months.
- +7 more secondary outcomes
Study Arms (2)
Afatinib 40 mg
EXPERIMENTALPatients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after being treated with platinum-based therapy took, orally, once daily one film-coated tablet of afatinib. Patients started with a 40 milligrams (mg) dose which could be escalated to 50 mg and/or reduced to 40 mg, 30 mg, or 20 mg, according to the absence of presence of drug-related adverse events (AEs).
Methotrexate 40 mg
ACTIVE COMPARATORPatients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after being treated with platinum-based therapy received once weekly an intravenous bolus injection of methotrexate. Patients started with a 40 milligrams (mg) per square meter of body surface area (m\^2) dose which could be escalated to 50 mg/m\^2 and/or reduced to 40 mg/m\^2, 30 mg/m\^2, or 20 mg/m\^2, according to the absence of presence of drug-related adverse events (AEs).
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy.
- Documented progressive disease based on investigator assessment according to RECIST, following receipt of a cisplatin and/or carboplatin and/or Nedaplatin based regimen administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy.
- Measurable disease according to RECIST (version 1.1).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Visit 2.
- Male and female patients age is 18 years or older
- Signed and dated written informed consent that is in compliance with ICH-GCP and local law.
You may not qualify if:
- Progressive disease within three months after completion of curatively intended treatment for locoregionally advanced or for metastatic head and neck squamous cell cancer (HNSCC).
- Primary tumour site nasopharynx (of any histology), sinuses, and/or salivary glands.
- Any other than one previous platinum based systemic regimen given for recurrent and/or metastatic disease, with the exception of immunotherapy used either before or after platinum based treatment. Re-challenge with the platinum based regimen after a temporary break is considered an additional line regimen only in case of progression within the break.
- Prior treatment with EGFR-targeted small molecules.
- Treatment with any investigational drug less than four weeks or anti-cancer therapy less than three weeks prior to randomization (except palliative radiotherapy to bones to alleviate pain).
- Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade \>2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade \>1 and/or diarrhoea CTCAE grade \>1 caused by prior treatment with EGFR targeted antibodies.
- Previous tumour bleeding CTCAE grade =3.
- Requirement for treatment with any of the prohibited concomitant medications.
- Major surgical or planned procedure less than four weeks prior to randomization (isolated biopsies are not considered as major surgical procedures).
- Any other malignancy unless free of disease for at least five years except for:
- Appropriately treated superficial basal cell skin cancer
- Surgically cured cervical cancer in situ
- For Korea: endoscopically cured superficial esophageal and/or gastric cancer is allowed
- Known lesion or signs of brain metastasis.
- Known pre-existing interstitial lung disease (ILD).
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (53)
Beijing Chao-Yang Hospital
Beijing, 100020, China
Cancer Hospital of Chinese Academy of Medical Science
Beijing, 100021, China
Navy General Hospital
Beijing, 100037, China
Peking Union Medical College Hospital
Beijing, 100730, China
The First Affiliated Hospital Of Bengbu Medical College
Bengbu, 233004, China
The First Hospital of Jilin University
Changchun, 130021, China
Sichuan Cancer Hospital
Chengdu, 610041, China
West China Hospital
Chengdu, 610042, China
Sun Yat-Sen University Cancer Center
Guangzhou, 510060, China
Zhejiang Cancer Hospital
Hangzhou, 310022, China
Harbin Medical University Cancer Hospital
Harbin, 150081, China
the 81th Hospital of PLA
Nanjing, 210002, China
Renji Hospital Shanghai Jiaotong Univesrity School of Medicine
Shanghai, 200001, China
Shanghai Changzheng Hospital
Shanghai, 200003, China
Shanghai Ninth People's Hospital
Shanghai, 200011, China
Fudan University Shanghai Cancer Center
Shanghai, 200032, China
Shanghai Ninth People's Hospital
Shanghai, 200125, China
Wuhan Union Hospital
Wuhan, 430022, China
Tongji Hospital, Tongji University
Wuhan, 430030, China
Alexandria Clinical Research Center
Alexandria, 21131, Egypt
National Cancer Institute, Cairo University
Cairo, 11796, Egypt
Mansoura University Faculty of Medicine
Dakahlia, 35516, Egypt
Pamela Youde Nethersole Eastern Hospital
Hong Kong, 999077, Hong Kong
Queen Mary Hospital
Hong Kong, 999077, Hong Kong
Prince of Wales Hospital
Shatin, 999077, Hong Kong
Sujan Surgical Cancer Hospital
Amravati, 444606, India
Pristine Hospital
Bengaluru, 560086, India
Acharya Tulsi Regional Cancer Treatment & Research Institute
Bikaner, 334001, India
Rajiv Gandhi Government General Hospital
Chennai, 600003, India
M N J Institute of Oncology and Regional Cancer Centre
Hyderabad, 500004, India
Geetanjali Medical College and Hospital
Jaipur, 313002, India
J K Cancer Institute
Kanpur, 208005, India
B. P .Poddar Hospital & Medical Research Ltd.
Kolkata, West Bengal, 700053, India
King George Medical University
Lucknow, 226003, India
Government Medical College & Hospital
Nagpur, 440009, India
Shatabdi Hospital, Nashik
Nashik, 422002, India
Ruby Hall Clinic
Pune, 411001, India
Noble Hospital Pvt Ltd
Pune, 411013, India
Perpetual Succour Hospital (Cebu)
Cebu City, 6000, Philippines
St. Luke's Medical Center
Quezon City, 1102, Philippines
National Cancer Center
Goyang, 10408, South Korea
Severance Hospital
Seoul, 120-752, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
The Catholic University of Korea, Seoul St.Mary's Hospital
Seoul, 137-701, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Keelung Chang Gung Memorial Lover's Lake Branch
Keelung, 204, Taiwan
Taichung Veterans General Hospital
Taichung, 407, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Tri-Service General Hospital
Taipei, 11490, Taiwan
Maharaj Nakom Chiangmai Hospital
Chiang Mai, 50200, Thailand
Srinagarind Hospital
Muang, 40002, Thailand
Naresuan University Hospital
Phitsanulok, 65000, Thailand
Songklanagarind Hospital
Songkhla, 90110, Thailand
Related Publications (1)
Guo Y, Ahn MJ, Chan A, Wang CH, Kang JH, Kim SB, Bello M, Arora RS, Zhang Q, He X, Li P, Dechaphunkul A, Kumar V, Kamble K, Li W, Kandil A, Cohen EEW, Geng Y, Zografos E, Tang PZ. Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial. Ann Oncol. 2019 Nov 1;30(11):1831-1839. doi: 10.1093/annonc/mdz388.
PMID: 31501887DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
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
May 15, 2013
First Posted
May 17, 2013
Study Start
June 7, 2013
Primary Completion
August 22, 2018
Study Completion
October 2, 2024
Last Updated
January 12, 2026
Results First Posted
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
- Access Criteria
- For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.