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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Placebo
* Drug: Afatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib (BIBW2992)<br>Once daily | Drug: Afatinib<br>* Once daily<br>|
| Placebo Comparator: Placebo<br>Once daily | Drug: Placebo<br>* Once daily<br>|

What is the study measuring?
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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 |