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: April 10, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Drug: Afatinib
Drug: Methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 483
Study Start Date: January 2012
Estimated Study Completion Date: July 2015
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Afatinib (BIBW 2992)
Once daily
Drug: Afatinib
Once daily
Active Comparator: Methotrexate
Weekly
Drug: Methotrexate
Weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01345682

  Show 98 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01345682     History of Changes
Other Study ID Numbers: 1200.43, 2011-000391-34
Study First Received: April 28, 2011
Results First Received: March 13, 2015
Last Updated: April 10, 2015
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
Czech Republic: State Institute for Drug Control
Denmark: The Danish Health and Medicines Authority
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Israel: Ministry of Health
Italy: Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Protection Against Health Risks
Russia: Pharmacological Committee, Ministry of Health
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 30, 2015