LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy

Boehringer Ingelheim483 enrolled

Overview

This randomised, open-label, phase III study will be performed in patients with R/M head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy. The objectives of the trial are to compare the efficacy and safety of afatinib versus methotrexate

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

483

Conditions

Head and Neck Neoplasms Carcinoma, Squamous Cell

Interventions

AfatinibDRUG

Once daily

MethotrexateDRUG

Weekly

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Histologically or cytologically confirmed R/M HNSCC of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy 2. Documented progressive disease based on investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) following receipt of at least two cycles of cisplatin or carboplatin administered for R/M disease 3. Measurable disease according to RECIST 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion criteria: 1. Progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC 2. Any other than one previous platinum based systemic regimen given for R/M disease 3. Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules 4. Pregnancy or breast feeding

Locations (101)

Outcomes

Primary Outcomes

Progression-free Survival (PFS) Based on Central Independent Review

PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016). The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied: * At least 20% increase in the Sum of Diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm * Appearance of one or more new lesions * Unequivocal progression of existing non-target lesions

Time frame: From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months

Secondary Outcomes

Overall Survival (OS)

Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive.

Time frame: From randomization until death or study completion date (06Dec2016); Up to 60 months

Objective Response (OR)

OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-Progressive Disease (PD) in NTL leads to PR * CR in TL, but not evaluated NTL leads to PR * PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; All the above scenarios should also satisfy 'No occurrence of new lesions'.

Data from ClinicalTrials.gov

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1200.43.00113 Boehringer Ingelheim Investigational Site

Harvey, Illinois, United States

1200.43.00106 Boehringer Ingelheim Investigational Site

Peoria, Illinois, United States

1200.43.00110 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

1200.43.00107 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

1200.43.00105 Boehringer Ingelheim Investigational Site

Stony Brook, New York, United States

1200.43.00102 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

1200.43.00103 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

1200.43.00109 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

1200.43.05401 Boehringer Ingelheim Investigational Site

Ciudad Autonoma de Bs As, Argentina

1200.43.05402 Boehringer Ingelheim Investigational Site

Santa Fe, Argentina

...and 91 more locations

Time frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

Disease Control (DC)

DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-PD in NTL leads to PR * CR in TL, but not evaluated NTL leads to PR * PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; SD for TL: change in the sum of diameters does not satisfy PR or PD. SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions.

Time frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

Tumour Shrinkage

Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis. Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase. Percentage of Participants with Tumour shrinkage as per the categories (\>=20% increase, \>=0 - \<20% increase, \>0 - \<30% decrease, \>=30 - \<50% decrease, \>=50% decrease) are presented.

Time frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date.