LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy

• ClinicalTrials.gov Identifier: NCT01345669
• Recruitment Status: Terminated
• First Posted: May 2, 2011
• Results First Posted: October 23, 2017
• Last Update Posted: December 7, 2017
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: April 28, 2011
• First Posted Date: May 2, 2011
• Results First Submitted Date: August 17, 2017
• Results First Posted Date: October 23, 2017
• Last Update Posted Date: December 7, 2017
• Actual Study Start Date: October 17, 2011
• Actual Primary Completion Date: September 12, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2017)

Disease Free Survival (DFS) [ Time Frame: Up to 5 years ]

Disease Free Survival defined as the time from randomisation until documented tumour recurrence/ second primary tumour (SPT) or death from any cause, whichever occurred first.

• Original Primary Outcome Measures (submitted: April 29, 2011): Disease Free Survival (DFS) [ Time Frame: Approximately 5 years ]

Current Secondary Outcome Measures (submitted: September 21, 2017)

• Disease Free Survival (DFS) Rate at 2 Years [ Time Frame: Up to 2 years ]
  Disease Free Survival (DFS) rate at 2 years. Probability of being disease free at 2 years in percentage is provided based on Kaplan-Meier method.
• Percentage of Patient Deaths (Overall Survival (OS)) [ Time Frame: Up to 5 years ]
  Overall survival (OS), defined as the time from randomisation until death (regardless of cause). Due to the small event rate in both treatment arms caused by the early termination of the trial, the hazard estimate is not interpretable. Hence presented the total randomized and the percentage of patients died.
• Patients With Improved Health Related Quality of Life (HRQOL) [ Time Frame: Up to 5 years ]
  HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Improvement was defined as a score that improved from baseline by at least 10 points (on the 0-100 point scale) at any time during the study. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the study. Patients who had neither improved nor worsened were considered as stable. Percentages of patients with improvement in HRQoL are presented.
• Time to Deterioration in Health Related Quality of Life (HRQOL) [ Time Frame: Up to 5 years ]
  HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Time to deterioration was defined as the time from randomisation to the first 10-point worsening on the 0-100 point scale. Patients with no deterioration (including those with disease recurrence/SPT) were censored at the last available HRQoL assessment date. Patients with no post-baseline assessments were censored on the day of randomisation.
• Health Related Quality of Life (HRQOL) Scores Over Time [ Time Frame: Baseline and 5 years ]
  HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Scoring of the symptom scales/items followed the European Organisation for Research and Treatment of Cancer (EORTC) scoring manual and a linear transformation of the scores to a 0-100 point scale. Higher values are better.

Original Secondary Outcome Measures (submitted: April 29, 2011)

• Changes in safety laboratory parameters [ Time Frame: Approximately 5 years ]
• DFS rate at 2 years [ Time Frame: Approximately 5 years ]
• Overall Survival (OS) [ Time Frame: Approximately 5 years ]
• Health Related Quality of Life (HRQOL) [ Time Frame: Approximately 5 years ]
• Incidence and intensity of adverse events [ Time Frame: Approximately 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Head and Neck Neoplasms

Intervention

• Drug: Placebo
  Once daily
• Drug: Afatinib
  Once daily

Study Arms

• Experimental: Afatinib (BIBW 2992)
  Once daily
  Intervention: Drug: Afatinib
• Placebo Comparator: Placebo
  Once daily
  Intervention: Drug: Placebo

Publications *

• Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, Romanov I, Vermorken J, Bourhis J, Tahara M, Martins Segalla JG, Psyrri A, Vasilevskaya I, Nangia CS, Chaves-Conde M, Kiyota N, Homma A, Holeckova P, Del Campo JM, Asarawala N, Nicolau UR, Rauch D, Even C, Wang B, Gibson N, Ehrnrooth E, Harrington K, Cohen EEW; LUX-Head & Neck 2 investigators. Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial. JAMA Oncol. 2019 Aug 1;5(8):1170-1180. doi: 10.1001/jamaoncol.2019.1146.
• Burtness B, Bourhis JP, Vermorken JB, Harrington KJ, Cohen EE. Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial. Trials. 2014 Nov 29;15:469. doi: 10.1186/1745-6215-15-469.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 21, 2017): 617
• Original Estimated Enrollment (submitted: April 29, 2011): 669
• Actual Study Completion Date: September 12, 2016
• Actual Primary Completion Date: September 12, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

1. Histologically or cytologically confirmed loco-regionally advanced head and neck squamous cell carcinoma (HNSCC), stage III to IVb
2. Unresected tumour prior to chemo-radiotherapy (CRT)
3. Concomitant CRT completed prior to randomisation
4. After concomitant platinum-based CRT, no evidence of disease (NED) on clinical and radiographic examinations
5. Eastern cooperative oncology group (ECOG) performance status 0 or 1

Exclusion criteria:

1. Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for HNSCC
2. 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
3. Any other malignancy (except for simultaneous HNSCC primaries, appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ) unless free of disease for at least five years
4. Known pre-existing Interstitial Lung Disease (ILD)
5. Pregnancy or breast feeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Denmark, Egypt, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Russian Federation, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic, Poland

Administrative Information

• NCT Number: NCT01345669
• Other Study ID Numbers: 1200.131; 2011-000392-14 ( EudraCT Number: EudraCT )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: November 2017