Clinical trial NCT01856478: 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
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
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-05-17
Enrollment: 340
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: up to 2 years
Secondary outcomes:
measure: Overall survival (OS), defined as the time from the date of randomization to the date of death (regardless of the cause of death)
timeFrame: up to 3 years
measure: Objective response defined as complete response (CR) or partial response (PR) determined by RECIST 1.1 according to the best response to study medication
timeFrame: up to 2 years
measure: Health related quality of life (HRQOL) will be assessed based on patient-reported questionaires
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
city: Beijing
country: China
facility: Cancer Hospital of Chinese Academy of Medical Science
city: Beijing
country: China
facility: Navy General Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital Of Bengbu Medical College
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing
country: China
facility: the 81th Hospital of PLA
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong Univesrity School of Medicine
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Wuhan
country: China
facility: Tongji Hospital, Tongji University
city: Alexandria
country: Egypt
facility: Alexandria Clinical Research Center
city: Cairo
country: Egypt
facility: National Cancer Institute, Cairo University
city: Dakahlia
country: Egypt
facility: Mansoura University Faculty of Medicine
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hongkong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Amravati
country: India
facility: Sujan Surgical Cancer Hospital
city: Bengaluru
country: India
facility: Pristine Hospital
city: Bikaner
country: India
facility: Acharya Tulsi Regional Cancer Treatment & Research Institute
city: Chennai
country: India
facility: Rajiv Gandhi Government General Hospital
city: Hyderabad
country: India
facility: M N J Institute of Oncology and Regional Cancer Centre
city: Jaipur
country: India
facility: Geetanjali Medical College and Hospital
city: Kanpur
country: India
facility: J K Cancer Institute
city: Kolkata, West Bengal
country: India
facility: B. P .Poddar Hospital & Medical Research Ltd.
city: Lucknow
country: India
facility: King George Medical University
city: Nagpur
country: India
facility: Government Medical College & Hospital
city: Nasik
country: India
facility: Shatabdi Hospital, Nashik
city: Pune
country: India
facility: Ruby Hall Clinic
city: Pune
country: India
facility: Noble Hospital Pvt Ltd
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital (Cebu)
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Keelung City
country: Taiwan
facility: Keelung Chang Gung Memorial Lover's Lake Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakom Chiangmai Hospital
city: Muang
country: Thailand
facility: Srinagarind Hospital
city: Phitsanulok
country: Thailand
facility: Naresuan University Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.