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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: afatinib; Drug: methotrexate

• Study Type: Interventional
• Enrollment (Actual): 340
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100020
    • Beijing Chao-Yang Hospital
  • Beijing, China, 100021
    • Cancer Hospital of Chinese Academy of Medical Science
  • Beijing, China, 100037
    • Navy General Hospital
  • Bengbu, China, 233004
    • The First affiliated hospital of bengbu medical college
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • The Second People's Hospital of Sichuan
  • Chengdu, China, 610042
    • West China Hospital
  • Guangzhou, China, 510060
    • Sun Yat-sen University Cancer Center
  • Haerbin, China, 150081
    • The Third Affiliated Hospital of Harbin Medical University
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Nanjing, China, 210002
    • the 81th Hospital of PLA
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200003
    • Shanghai ChangZheng hospital
  • Shanghai, China, 200011
    • Shanghai Ninth People's Hospital
  • Shanghai, China, 200001
    • Renji Hospital Shanghai Jiaotong Univesrity School of Medicine
  • Shanghai, China, 200125
    • Shanghai Ninth People's Hospital
  • Wuhan, China, 430022
    • Wuhan Union Hospital
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji University
• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria Clinical Research Center
  • Cairo, Egypt, 11796
    • National Cancer Institute, Cairo University
  • Dakahlia, Egypt, 35516
    • Mansoura University Faculty of Medicine
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Pamela Youde Nethersole Eastern Hospital
  • Hongkong, Hong Kong, 999077
    • Queen Mary Hospital
  • Shatin, Hong Kong, 999077
    • Prince of Wales Hospital
• India
  • Amravati, India, 444606
    • Sujan Surgical Cancer Hospital
  • Bengaluru, India, 560086
    • Pristine Hospital
  • Bikaner, India, 334001
    • Acharya Tulsi Regional Cancer Treatment & Research Institute
  • Chennai, India, 600003
    • Rajiv Gandhi Government General Hospital
  • Hyderabad, India, 500004
    • M N J Institute of Oncology and Regional Cancer Centre
  • Jaipur, India, 313002
    • Geetanjali Medical College and Hospital
  • Kanpur, India, 208005
    • J K Cancer Institute
  • Kolkata, West Bengal, India, 700053
    • B. P .Poddar Hospital & Medical Research Ltd.
  • Lucknow, India, 226003
    • King George Medical University
  • Nagpur, India, 440009
    • Government Medical College & Hospital
  • Nasik, India, 422002
    • Shatabdi Hospital, Nashik
  • Pune, India, 411013
    • Noble Hospital Pvt Ltd
  • Pune, India, 411001
    • Ruby Hall Clinic
• Korea, Republic of
  • Goyang, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea, Seoul St.Mary's Hospital
• Philippines
  • Cebu City, Philippines, 6000
    • Perpetual Succour Hospital (Cebu)
  • Quezon City, Philippines, 1102
    • St. Luke's Medical Center
• Taiwan
  • Keelung City, Taiwan, 204
    • Keelung Chang Gung Memorial Lover's Lake Branch
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
• Thailand
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakom Chiangmai Hospital
  • Muang, Thailand, 40002
    • Srinagarind Hospital
  • Phitsanulok, Thailand, 65000
    • Naresuan University Hospital
  • Songkla, Thailand, 90110
    • Songklanagarind Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• 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.

Exclusion criteria:

• 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:

  • Other HNSCC of a location as described in inclusion criterion number 1
  • 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).
• Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification =III, unstable angina, myocardial infarction within six months prior to randomization, or poorly controlled arrhythmia.
• Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom in the opinion of the investigator, e.g. Crohn's disease, malabsorption or CTCAE grade >1 diarrhoea of any aetiology at randomization.
• Known HIV, active hepatitis B, active hepatitis C, and/or other known severe infections, including but not limited to tuberculosis, as judged by the investigator.
• Other significant disease that in the investigator's opinion would exclude the subject from the trial.

• Screening laboratory values:

  • Absolute neutrophil count (ANC) <1.5x10^9/l
  • Platelet count <75x10^9/l
  • Total bilirubin >1.5 times the upper limit of normal (ULN)
  • Aspartate amino transferase (AST) or alanine amino transferase (ALT) >3 times the ULN (if related to liver metastases >5 times the ULN)
  • Calculated creatinine clearance <50 ml/min (as evidenced by using the Cockcroft-Gault formula).
• Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or to use adequate contraception during the trial and for at least six months after end of treatment. Adequate methods of contraception and definition of child-bearing potential.
• Pregnancy or breast feeding.
• Known or suspected hypersensitivity to any of the study medications or their excipients.
• Patients unable to comply with the protocol, in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: afatinib; oral intake, once daily	Drug: afatinib; oral intake, once daily
Active Comparator: methotrexate; intravenous bolus injection, once weekly	Drug: methotrexate; intravenous bolus injection, once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression free survival (PFS), defined as the time from the date of randomization to the date of progression evaluated according to RECIST 1.1 or to the date of death, whichever occurs first	up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS), defined as the time from the date of randomization to the date of death (regardless of the cause of death)	up to 3 years
Objective response defined as complete response (CR) or partial response (PR) determined by RECIST 1.1 according to the best response to study medication	up to 2 years
Health related quality of life (HRQOL) will be assessed based on patient-reported questionaires	up to 2 years

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2013
• Primary Completion (Actual): August 22, 2018
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: May 15, 2013
• First Submitted That Met QC Criteria: May 15, 2013
• First Posted (Estimated): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Protein Kinase Inhibitors; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Methotrexate; Afatinib
• Other Study ID Numbers: 1200.161; 1200-0161 (Other Identifier: Boehringer Ingelheim)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this 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".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to 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.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing 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 both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR