Head and Neck Neoplasms
Conditions
Brief summary
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.
Interventions
DRUGPlacebo
Once daily
DRUGAfatinib
Once daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | up to 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) Rate at 2 Years | up to 2 years | Disease Free Survival (DFS) rate at 2 years is presented |
| Overall Survival (OS) | up to 4 years | 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. |
| Health Related Quality of Life (HRQOL) | up to 4 years | 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 |
Countries
China, Singapore, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Afatinib (BIBW2992) Afatinib (BIBW2992) is a film coated tablet. Patients were administered single daily dose of afatinib, starting at 40 milligram (mg) orally with water (\
250 millilitre) up to a period of 80 weeks. The dose had to be escalated to 50 mg and/or reduced to 40 mg, 30 mg, or 20 mg. | 25 |
| Placebo Single daily dose of matching placebo available for the 50 mg, 40 mg, 30 mg and 20 mg afatinib tablets were administered orally with water (\
250 millilitre) up to a period of 80 weeks. | 11 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Primary tumour recurrence | 2 | 1 |
| Overall Study | Refused to continue study medication | 1 | 0 |
| Overall Study | Study early termination | 20 | 10 |
| Overall Study | Treatment completed | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Afatinib (BIBW2992) | Placebo |
|---|---|---|---|
| Age, Continuous | 56.3 Years STANDARD_DEVIATION 8.82 | 55.4 Years STANDARD_DEVIATION 9.7 | 58.4 Years STANDARD_DEVIATION 6.27 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 35 Participants | 25 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 11 | 24 / 25 |
| serious Total, serious adverse events | 3 / 11 | 5 / 25 |
Outcome results
Primary
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.
Time frame: up to 4 years
Population: Randomised Set; This study was early terminated and data was available for less than 2/3rds of participants hence per internal Boehringer Ingelheim rules the analysis was not performed as planned in protocol.
Secondary
Disease Free Survival (DFS) Rate at 2 Years
Disease Free Survival (DFS) rate at 2 years is presented
Time frame: up to 2 years
Population: Randomised Set; This study was early terminated and data was available for less than 2/3rds of participants hence per internal Boehringer Ingelheim rules the analysis was not performed as planned in protocol.
Secondary
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
Time frame: up to 4 years
Population: Randomised Set; This study was early terminated and data was available for less than 2/3rds of participants hence per internal Boehringer Ingelheim rules the analysis was not performed as planned in protocol.
Secondary
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.
Time frame: up to 4 years
Population: Randomised Set; This study was early terminated and data was available for less than 2/3rds of participants hence per internal Boehringer Ingelheim rules the analysis was not performed as planned in protocol.