LUX-Head & Neck 4: Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy

A Randomised, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of Afatinib (BIBW 2992) as Adjuvant Therapy After Chemo-radiotherapy in Primary Unresected Patients With Stage III, IVa, or IVb Loco-regionally Advanced Head and Neck Squamous Cell Carcinoma

This randomised, double-blind phase III trial will be performed in patients with head and neck squamous cell carcinoma (HNSCC). The objectives of the trial are to compare the efficacy and safety of afatinib (BIBW 2992) with placebo as adjuvant therapy to patients who have received definitive chemo-radiotherapy.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: Placebo; Drug: Afatinib

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 1200.162.86010 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1200.162.86012 Boehringer Ingelheim Investigational Site
  • Changchun, China
    • 1200.162.86019 Boehringer Ingelheim Investigational Site
  • Chengdu, China
    • 1200.162.86007 Boehringer Ingelheim Investigational Site
  • Fuzhou, China
    • 1200.162.86017 Boehringer Ingelheim Investigational Site
  • Guangzhou, China
    • 1200.162.86005 Boehringer Ingelheim Investigational Site
  • Hangzhou, China
    • 1200.162.86003 Boehringer Ingelheim Investigational Site
  • Jinan, China
    • 1200.162.86013 Boehringer Ingelheim Investigational Site
  • Nanning, China
    • 1200.162.86014 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1200.162.86001 Boehringer Ingelheim Investigational Site
  • Tianjin, China
    • 1200.162.86020 Boehringer Ingelheim Investigational Site
  • Wuhan, China
    • 1200.162.86004 Boehringer Ingelheim Investigational Site
  • Wuhan, China
    • 1200.162.86018 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of
    • 1200.162.82001 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1200.162.82002 Boehringer Ingelheim Investigational Site
• Singapore
  • Singapore, Singapore
• Taiwan
  • Keelung City, Taiwan
    • 1200.162.88603 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Histologically or cytologically confirmed loco-regionally advanced head and neck squamous cell carcinoma (HNSCC), stage III to IVb
• Unresected tumour prior to chemo-radiotherapy (CRT)
• Concomitant CRT completed prior to randomisation
• After concomitant platinum-based CRT, no evidence of disease (NED) on clinical and radiographic examinations
• Eastern cooperative oncology group (ECOG) performance status 0 or 1

Exclusion criteria:

• Patients with smoking history of less than or equal to 10 pack years and with primary tumour site of base of tongue and/or tonsil
• Cancer of nasopharynx, sinuses, and/or salivary glands
• Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for HNSCC
• Known pre-existing Interstitial Lung Disease (ILD)
• Any past or present history of areca/betel-nut chewing or its derivatives for a cumulative duration of more than 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Once daily	Drug: Placebo; Once daily
Experimental: Afatinib (BIBW2992); Once daily	Drug: Afatinib; Once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	DFS, defined as the number of days from the date of randomisation to the date of tumour recurrence/ Second Primary Tumours (SPT) or death from any cause, whichever occurred first. For patients with known date of tumour recurrence/SPT (or death), the event date was the date of tumour recurrence/SPT or the date of death, whichever came first, i.e. DFS [day] = minimum (date of tumour recurrence/SPT, date of death) - date of randomisation +1. For patients known to be alive and without tumour recurrence/SPT by the end of trial or follow-up visit, they were censored at the date of last imaging when the patient was known to be disease-free and alive: DFS (censored) [days] = date of last imaging when the patient was known to be diseasefree and alive - date of randomisation + 1. The Kaplan-Meier (KM) method was to be used to estimate the median DFS for each treatment group. 95% confidence interval (CI) was to be constructed using the Greenwood variance estimate.	up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS) Rate at 2 Years	Disease Free Survival (DFS) rate at 2 years is presented	up to 2 years
Overall Survival (OS)	OS was defined as time from the date of randomisation until death. For patients with known date of death (regardless of the cause of death): OS [days] = date of death - date of randomisation +1 For patients known to be alive by the end of trial: OS (censored) [days] = the last date when the patient was known to be alive - date of randomisation +1 OS was to be analysed similarly to DFS.	up to 4 years
Health Related Quality of Life (HRQOL)	The main analysis of HRQOL questionnaires was to focus on the change in score from baseline in the following scales measured on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-H&N35: Global Health Status/ Quality of Life (QOL) Scale; Pain Scale; Swallowing Scale	up to 4 years

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2014
• Primary Completion (Actual): August 22, 2016
• Study Completion (Actual): August 22, 2016

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (Estimate): May 6, 2014

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.162