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

Head and Neck Neoplasms Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01856478
• Other study ID #: 1200.161
• Secondary ID: 1200-0161
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 23, 2013
• Est. completion date: August 31, 2024

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 340
• Est. completion date: August 31, 2024
• Est. primary completion date: August 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Neoplasms

Intervention

Drug:
• methotrexate
intravenous bolus injection, once weekly
• afatinib
oral intake, once daily

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital	Beijing
China	Cancer Hospital of Chinese Academy of Medical Science	Beijing
China	Navy General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	The First Affiliated Hospital Of Bengbu Medical College	Bengbu
China	The First Hospital of Jilin University	Changchun
China	The Second People's Hospital of Sichuan	Chengdu
China	West China Hospital	Chengdu
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	The Third Affiliated Hospital of Harbin Medical University	Haerbin
China	Zhejiang Cancer Hospital	Hangzhou
China	the 81th Hospital of PLA	Nanjing
China	Fudan University Shanghai Cancer Center	Shanghai
China	Renji Hospital Shanghai Jiaotong Univesrity School of Medicine	Shanghai
China	Shanghai Changzheng Hospital	Shanghai
China	Shanghai Ninth People's Hospital	Shanghai
China	Shanghai Ninth People's Hospital	Shanghai
China	Tongji Hospital, Tongji University	Wuhan
China	Wuhan Union Hospital	Wuhan
Egypt	Alexandria Clinical Research Center	Alexandria
Egypt	National Cancer Institute, Cairo University	Cairo
Egypt	Mansoura University Faculty of Medicine	Dakahlia
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hongkong
Hong Kong	Prince of Wales Hospital	Shatin
India	Sujan Surgical Cancer Hospital	Amravati
India	Pristine Hospital	Bengaluru
India	Acharya Tulsi Regional Cancer Treatment & Research Institute	Bikaner
India	Rajiv Gandhi Government General Hospital	Chennai
India	M N J Institute of Oncology and Regional Cancer Centre	Hyderabad
India	Geetanjali Medical College and Hospital	Jaipur
India	J K Cancer Institute	Kanpur
India	B. P .Poddar Hospital & Medical Research Ltd.	Kolkata, West Bengal
India	King George Medical University	Lucknow
India	Government Medical College & Hospital	Nagpur
India	Shatabdi Hospital, Nashik	Nasik
India	Noble Hospital Pvt Ltd	Pune
India	Ruby Hall Clinic	Pune
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul
Philippines	Perpetual Succour Hospital (Cebu)	Cebu City
Philippines	St. Luke's Medical Center	Quezon City
Taiwan	Keelung Chang Gung Memorial Lover's Lake Branch	Keelung City
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Thailand	Maharaj Nakom Chiangmai Hospital	Chiang Mai
Thailand	Srinagarind Hospital	Muang
Thailand	Naresuan University Hospital	Phitsanulok
Thailand	Songklanagarind Hospital	Songkla

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

China,  Egypt,  Hong Kong,  India,  Korea, Republic of,  Philippines,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Health related quality of life (HRQOL) will be assessed based on patient-reported questionaires		up to 2 years

External Links

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