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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01345682
First received: April 28, 2011
Last updated: October 17, 2016
Last verified: October 2016

April 28, 2011
October 17, 2016
January 2012
March 2014   (final data collection date for primary outcome measure)
Progression-free Survival (PFS) Based on Central Independent Review [ Time Frame: From randomization until disease progression, death or data cut-off (07May2014); Up to 28 months ] [ Designated as safety issue: No ]

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 cut-off date (7 May 2014).

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 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
The primary efficacy endpoint of the trial is progression free survival (PFS) [ Time Frame: Approximately 9 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01345682 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: From randomization until death or data cut-off (30Jun2014); Up to 29 months ] [ Designated as safety issue: No ]
    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 cut-off date (30 Jun 2014) were to be censored on the date that they were last known to be alive.
  • Objective Response (OR) [ Time Frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (Up to 28 months) ] [ Designated as safety issue: No ]

    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-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'.

  • Disease Control (DC) [ Time Frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (Up to 28 months) ] [ Designated as safety issue: No ]

    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.

  • Tumour Shrinkage [ Time Frame: Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (Up to 28 months) ] [ Designated as safety issue: No ]

    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.

  • Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]

    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.

  • Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]

    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.

  • Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]

    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.

  • Status Change in Pain Scale [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
  • Status Change in Swallowing Scale [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
  • Status Change in Global Health Status Scale [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
  • Time to Deterioration in Pain [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
  • Time to Deterioration in Swallowing [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
  • Time to Deterioration in Global Health Status [ Time Frame: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. ] [ Designated as safety issue: No ]
    The time to deterioration was defined as the time from randomisation to a score decreased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
  • Changes in safety laboratory parameters [ Time Frame: Approximately 9 months ] [ Designated as safety issue: Yes ]
  • Overall survival (OS) is the key secondary endpoint [ Time Frame: Approximately 9 months ] [ Designated as safety issue: No ]
  • Objective response based on RECIST [ Time Frame: Approximately 9 months ] [ Designated as safety issue: No ]
  • Health related quality of life (HRQOL) [ Time Frame: Approximately 9 months ] [ Designated as safety issue: No ]
  • Incidence and intensity of adverse events [ Time Frame: Approximately 9 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
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
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
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Head and Neck Neoplasms
  • Carcinoma, Squamous Cell
  • Drug: Afatinib
    Once daily
  • Drug: Methotrexate
    Weekly
  • Experimental: Afatinib (BIBW 2992)
    Once daily
    Intervention: Drug: Afatinib
  • Active Comparator: Methotrexate
    Weekly
    Intervention: Drug: Methotrexate
Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators.. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):583-94. doi: 10.1016/S1470-2045(15)70124-5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
483
January 2017
March 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Austria,   Belgium,   Brazil,   Czech Republic,   Denmark,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Mexico,   Russian Federation,   South Africa,   Spain,   Sweden,   Switzerland
 
NCT01345682
1200.43, 2011-000391-34
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP