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
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Terminated
CT.gov ID
NCT01345669
Collaborator
(none)
617
162
2
58.9
3.8
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
617 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Oct 17, 2011
Actual Primary Completion Date
:
Sep 12, 2016
Actual Study Completion Date
:
Sep 12, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Afatinib (BIBW 2992) Once daily |
Drug: Afatinib
Once daily
|
| Placebo Comparator: Placebo Once daily |
Drug: Placebo
Once daily
|
Outcome Measures
Primary Outcome Measures
- Disease Free Survival (DFS) [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.
Secondary Outcome Measures
- Disease Free Survival (DFS) Rate at 2 Years [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)) [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) [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) [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 [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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:
-
Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for HNSCC
-
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
-
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
-
Known pre-existing Interstitial Lung Disease (ILD)
-
Pregnancy or breast feeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1200.131.00171 Boehringer Ingelheim Investigational Site | Little Rock | Arkansas | United States | |
| 2 | 1200.131.00181 Boehringer Ingelheim Investigational Site | Orange | California | United States | |
| 3 | 1200.131.00177 Boehringer Ingelheim Investigational Site | Aurora | Colorado | United States | |
| 4 | 1200.131.00185 Boehringer Ingelheim Investigational Site | New Haven | Connecticut | United States | |
| 5 | 1200.131.00173 Boehringer Ingelheim Investigational Site | Baltimore | Maryland | United States | |
| 6 | 1200.131.00176 Boehringer Ingelheim Investigational Site | Boston | Massachusetts | United States | |
| 7 | 1200.131.00182 Boehringer Ingelheim Investigational Site | Omaha | Nebraska | United States | |
| 8 | 1200.131.00175 Boehringer Ingelheim Investigational Site | Lebanon | New Hampshire | United States | |
| 9 | 1200.131.00179 Boehringer Ingelheim Investigational Site | Stony Brook | New York | United States | |
| 10 | 1200.131.00188 Boehringer Ingelheim Investigational Site | The Bronx | New York | United States | |
| 11 | 1200.131.10200 Boehringer Ingelheim Investigational Site | Winston-Salem | North Carolina | United States | |
| 12 | 1200.131.00172 Boehringer Ingelheim Investigational Site | Philadelphia | Pennsylvania | United States | |
| 13 | 1200.131.00184 Boehringer Ingelheim Investigational Site | San Antonio | Texas | United States | |
| 14 | 1200.131.00198 Boehringer Ingelheim Investigational Site | Spokane Valley | Washington | United States | |
| 15 | 1200.131.00183 Boehringer Ingelheim Investigational Site | Wenatchee | Washington | United States | |
| 16 | 1200.131.05451 Boehringer Ingelheim Investigational Site | Ciudad Autonoma de Bs As | Argentina | ||
| 17 | 1200.131.05457 Boehringer Ingelheim Investigational Site | Cordoba | Argentina | ||
| 18 | 1200.131.05458 Boehringer Ingelheim Investigational Site | San Miguel de Tucuman | Argentina | ||
| 19 | 1200.131.05452 Boehringer Ingelheim Investigational Site | Santa Fe | Argentina | ||
| 20 | 1200.131.05453 Boehringer Ingelheim Investigational Site | Villa Dominico | Argentina | ||
| 21 | 1200.131.06151 Boehringer Ingelheim Investigational Site | Wooloongabba | Queensland | Australia | |
| 22 | 1200.131.04353 Boehringer Ingelheim Investigational Site | Leoben | Austria | ||
| 23 | 1200.131.04357 Boehringer Ingelheim Investigational Site | Linz | Austria | ||
| 24 | 1200.131.04355 Boehringer Ingelheim Investigational Site | Salzburg | Austria | ||
| 25 | 1200.131.04351 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 26 | 1200.131.04359 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 27 | 1200.131.03259 Boehringer Ingelheim Investigational Site | Brussel | Belgium | ||
| 28 | 1200.131.03256 Boehringer Ingelheim Investigational Site | Charleroi | Belgium | ||
| 29 | 1200.131.03255 Boehringer Ingelheim Investigational Site | Hasselt | Belgium | ||
| 30 | 1200.131.03253 Boehringer Ingelheim Investigational Site | Kortrijk | Belgium | ||
| 31 | 1200.131.03252 Boehringer Ingelheim Investigational Site | Liège | Belgium | ||
| 32 | 1200.131.03254 Boehringer Ingelheim Investigational Site | Liège | Belgium | ||
| 33 | 1200.131.03258 Boehringer Ingelheim Investigational Site | Namur | Belgium | ||
| 34 | 1200.131.05554 Boehringer Ingelheim Investigational Site | Barretos | Brazil | ||
| 35 | 1200.131.05555 Boehringer Ingelheim Investigational Site | Jau | Brazil | ||
| 36 | 1200.131.05557 Boehringer Ingelheim Investigational Site | Passo Fundo | Brazil | ||
| 37 | 1200.131.05553 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil | ||
| 38 | 1200.131.05551 Boehringer Ingelheim Investigational Site | Sao Paulo | Brazil | ||
| 39 | 1200.131.05556 Boehringer Ingelheim Investigational Site | Sao Paulo | Brazil | ||
| 40 | 1200.131.00152 Boehringer Ingelheim Investigational Site | Vancouver | British Columbia | Canada | |
| 41 | 1200.131.00157 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada | |
| 42 | 1200.131.00151 Boehringer Ingelheim Investigational Site | Windsor | Ontario | Canada | |
| 43 | 1200.131.00153 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 44 | 1200.131.00154 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 45 | 1200.131.00155 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 46 | 1200.131.05652 Boehringer Ingelheim Investigational Site | Vina De Mar | Chile | ||
| 47 | 1200.131.05651 Boehringer Ingelheim Investigational Site | Vina del Mar | Chile | ||
| 48 | 1200.131.04254 Boehringer Ingelheim Investigational Site | Brno | Czechia | ||
| 49 | 1200.131.04253 Boehringer Ingelheim Investigational Site | Praha 5 | Czechia | ||
| 50 | 1200.131.04251 Boehringer Ingelheim Investigational Site | Praha 8 | Czechia | ||
| 51 | 1200.131.04551 Boehringer Ingelheim Investigational Site | København Ø | Denmark | ||
| 52 | 1200.131.2052 Boehringer Ingelheim Investigational Site | Alexandria | Egypt | ||
| 53 | 1200.131.35851 Boehringer Ingelheim Investigational Site | Turku | Finland | ||
| 54 | 1200.131.03353 Boehringer Ingelheim Investigational Site | Le Havre | France | ||
| 55 | 1200.131.03362 Boehringer Ingelheim Investigational Site | Marseille Cedex 5 | France | ||
| 56 | 1200.131.03359 Boehringer Ingelheim Investigational Site | Nice cedex 2 | France | ||
| 57 | 1200.131.03365 Boehringer Ingelheim Investigational Site | Orléans Cedex 2 | France | ||
| 58 | 1200.131.03355 Boehringer Ingelheim Investigational Site | Pierre-Bénite | France | ||
| 59 | 1200.131.03367 Boehringer Ingelheim Investigational Site | Rouen | France | ||
| 60 | 1200.131.03370 Boehringer Ingelheim Investigational Site | Saint Cloud | France | ||
| 61 | 1200.131.03354 Boehringer Ingelheim Investigational Site | Saint Herblain Cedex | France | ||
| 62 | 1200.131.03369 Boehringer Ingelheim Investigational Site | Saint Priest en Jarez | France | ||
| 63 | 1200.131.03366 Boehringer Ingelheim Investigational Site | Salouel | France | ||
| 64 | 1200.131.03356 Boehringer Ingelheim Investigational Site | Tours | France | ||
| 65 | 1200.131.03357 Boehringer Ingelheim Investigational Site | Villejuif Cedex | France | ||
| 66 | 1200.131.04954 Boehringer Ingelheim Investigational Site | Essen | Germany | ||
| 67 | 1200.131.04961 Boehringer Ingelheim Investigational Site | Freiburg | Germany | ||
| 68 | 1200.131.04953 Boehringer Ingelheim Investigational Site | Hannover | Germany | ||
| 69 | 1200.131.04956 Boehringer Ingelheim Investigational Site | Jena | Germany | ||
| 70 | 1200.131.04959 Boehringer Ingelheim Investigational Site | Kaiserslautern | Germany | ||
| 71 | 1200.131.04951 Boehringer Ingelheim Investigational Site | Leipzig | Germany | ||
| 72 | 1200.131.04957 Boehringer Ingelheim Investigational Site | Rostock | Germany | ||
| 73 | 1200.131.04964 Boehringer Ingelheim Investigational Site | Trier | Germany | ||
| 74 | 1200.131.04963 Boehringer Ingelheim Investigational Site | Ulm | Germany | ||
| 75 | 1200.131.04962 Boehringer Ingelheim Investigational Site | Villingen-Schwenningen | Germany | ||
| 76 | 1200.131.03054 Boehringer Ingelheim Investigational Site | Chaidari | Greece | ||
| 77 | 1200.131.03052 Boehringer Ingelheim Investigational Site | Thessaloniki | Greece | ||
| 78 | 1200.131.03651 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 79 | 1200.131.03652 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 80 | 1200.131.03656 Boehringer Ingelheim Investigational Site | Budpest | Hungary | ||
| 81 | 1200.131.03654 Boehringer Ingelheim Investigational Site | Debrecen | Hungary | ||
| 82 | 1200.131.03655 Boehringer Ingelheim Investigational Site | Kecskemet | Hungary | ||
| 83 | 1200.131.09178 Boehringer Ingelheim Investigational Site | Ahmadabad | India | ||
| 84 | 1200.131.09165 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 85 | 1200.131.09152 Boehringer Ingelheim Investigational Site | Bikaner | India | ||
| 86 | 1200.131.09163 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 87 | 1200.131.09173 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 88 | 1200.131.09179 Boehringer Ingelheim Investigational Site | Delhi | India | ||
| 89 | 1200.131.09170 Boehringer Ingelheim Investigational Site | Gurgaon | India | ||
| 90 | 1200.131.09180 Boehringer Ingelheim Investigational Site | Hyderabad | India | ||
| 91 | 1200.131.09172 Boehringer Ingelheim Investigational Site | Jaipur | India | ||
| 92 | 1200.131.09176 Boehringer Ingelheim Investigational Site | Karamsad,Anand, Gujarat | India | ||
| 93 | 1200.131.09162 Boehringer Ingelheim Investigational Site | Madurai, Tamil Nadu | India | ||
| 94 | 1200.131.09175 Boehringer Ingelheim Investigational Site | Mazagaon, Mumbai | India | ||
| 95 | 1200.131.09151 Boehringer Ingelheim Investigational Site | New Delhi | India | ||
| 96 | 1200.131.09164 Boehringer Ingelheim Investigational Site | Pune | India | ||
| 97 | 1200.131.09159 Boehringer Ingelheim Investigational Site | Vishakapatnam | India | ||
| 98 | 1200.131.97251 Boehringer Ingelheim Investigational Site | Haifa | Israel | ||
| 99 | 1200.131.97253 Boehringer Ingelheim Investigational Site | Petach Tikva | Israel | ||
| 100 | 1200.131.03957 Boehringer Ingelheim Investigational Site | Confreria (CN) | Italy | ||
| 101 | 1200.131.03951 Boehringer Ingelheim Investigational Site | Milano | Italy | ||
| 102 | 1200.131.03955 Boehringer Ingelheim Investigational Site | Milano | Italy | ||
| 103 | 1200.131.03960 Boehringer Ingelheim Investigational Site | Milano | Italy | ||
| 104 | 1200.131.08156 Boehringer Ingelheim Investigational Site | Aichi, Nagoya | Japan | ||
| 105 | 1200.131.08153 Boehringer Ingelheim Investigational Site | Chiba, Kashiwa | Japan | ||
| 106 | 1200.131.08151 Boehringer Ingelheim Investigational Site | Hokkaido, Sapporo | Japan | ||
| 107 | 1200.131.08161 Boehringer Ingelheim Investigational Site | Hyogo, Akashi | Japan | ||
| 108 | 1200.131.08157 Boehringer Ingelheim Investigational Site | Hyogo, Kobe | Japan | ||
| 109 | 1200.131.08159 Boehringer Ingelheim Investigational Site | Kanagawa, Isehara | Japan | ||
| 110 | 1200.131.08164 Boehringer Ingelheim Investigational Site | Miyagi, Natori | Japan | ||
| 111 | 1200.131.08160 Boehringer Ingelheim Investigational Site | Osaka, Osaka | Japan | ||
| 112 | 1200.131.08155 Boehringer Ingelheim Investigational Site | Shizuoka, Sunto-gun | Japan | ||
| 113 | 1200.131.08152 Boehringer Ingelheim Investigational Site | Tochigi, Shimotsuke | Japan | ||
| 114 | 1200.131.08163 Boehringer Ingelheim Investigational Site | Tokyo, Koto-ku | Japan | ||
| 115 | 1200.131.08154 Boehringer Ingelheim Investigational Site | Tokyo, Meguro-ku | Japan | ||
| 116 | 1200.131.05252 Boehringer Ingelheim Investigational Site | Mexico | Mexico | ||
| 117 | 1200.131.03152 Boehringer Ingelheim Investigational Site | Amsterdam | Netherlands | ||
| 118 | 1200.131.03153 Boehringer Ingelheim Investigational Site | Leiden | Netherlands | ||
| 119 | 1200.131.03151 Boehringer Ingelheim Investigational Site | Rotterdam | Netherlands | ||
| 120 | 1200.131.35155 Boehringer Ingelheim Investigational Site | Almada | Portugal | ||
| 121 | 1200.131.35154 Boehringer Ingelheim Investigational Site | Coimbra | Portugal | ||
| 122 | 1200.131.35153 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 123 | 1200.131.35151 Boehringer Ingelheim Investigational Site | Porto | Portugal | ||
| 124 | 1200.131.35152 Boehringer Ingelheim Investigational Site | Évora | Portugal | ||
| 125 | 1200.131.00759 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 126 | 1200.131.00753 Boehringer Ingelheim Investigational Site | Omsk | Russian Federation | ||
| 127 | 1200.131.00760 Boehringer Ingelheim Investigational Site | Pyatigorsk | Russian Federation | ||
| 128 | 1200.131.00761 Boehringer Ingelheim Investigational Site | Pyatigorsk | Russian Federation | ||
| 129 | 1200.131.00763 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 130 | 1200.131.00755 Boehringer Ingelheim Investigational Site | Ufa | Russian Federation | ||
| 131 | 1200.131.00762 Boehringer Ingelheim Investigational Site | Ufa | Russian Federation | ||
| 132 | 1200.131.03451 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 133 | 1200.131.03454 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 134 | 1200.131.03463 Boehringer Ingelheim Investigational Site | Girona | Spain | ||
| 135 | 1200.131.03452 Boehringer Ingelheim Investigational Site | Hospitalet de Llobregat | Spain | ||
| 136 | 1200.131.03459 Boehringer Ingelheim Investigational Site | Lugo | Spain | ||
| 137 | 1200.131.03457 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 138 | 1200.131.03464 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 139 | 1200.131.03465 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 140 | 1200.131.03456 Boehringer Ingelheim Investigational Site | Málaga | Spain | ||
| 141 | 1200.131.03462 Boehringer Ingelheim Investigational Site | Málaga | Spain | ||
| 142 | 1200.131.03455 Boehringer Ingelheim Investigational Site | Pamplona | Spain | ||
| 143 | 1200.131.03460 Boehringer Ingelheim Investigational Site | Pozuelo De Alarcón, Madrid | Spain | ||
| 144 | 1200.131.03466 Boehringer Ingelheim Investigational Site | Sevilla | Spain | ||
| 145 | 1200.131.03458 Boehringer Ingelheim Investigational Site | Zaragoza | Spain | ||
| 146 | 1200.131.03461 Boehringer Ingelheim Investigational Site | Ávila | Spain | ||
| 147 | 1200.131.04652 Boehringer Ingelheim Investigational Site | Göteborg | Sweden | ||
| 148 | 1200.131.04651 Boehringer Ingelheim Investigational Site | Stockholm | Sweden | ||
| 149 | 1200.131.04151 Boehringer Ingelheim Investigational Site | Basel | Switzerland | ||
| 150 | 1200.131.04152 Boehringer Ingelheim Investigational Site | Bern | Switzerland | ||
| 151 | 1200.131.03854 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 152 | 1200.131.03851 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 153 | 1200.131.04456 Boehringer Ingelheim Investigational Site | Denbighshire | United Kingdom | ||
| 154 | 1200.131.04455 Boehringer Ingelheim Investigational Site | Edinburgh | United Kingdom | ||
| 155 | 1200.131.04459 Boehringer Ingelheim Investigational Site | Exeter | United Kingdom | ||
| 156 | 1200.131.04460 Boehringer Ingelheim Investigational Site | Glasgow | United Kingdom | ||
| 157 | 1200.131.04453 Boehringer Ingelheim Investigational Site | Leicester | United Kingdom | ||
| 158 | 1200.131.04451 Boehringer Ingelheim Investigational Site | London | United Kingdom | ||
| 159 | 1200.131.04452 Boehringer Ingelheim Investigational Site | Manchester | United Kingdom | ||
| 160 | 1200.131.04454 Boehringer Ingelheim Investigational Site | Sheffield | United Kingdom | ||
| 161 | 1200.131.04458 Boehringer Ingelheim Investigational Site | Sutton | United Kingdom | ||
| 162 | 1200.131.04457 Boehringer Ingelheim Investigational Site | Whitchurch, Cardiff | United Kingdom |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01345669
Other Study ID Numbers:
- 1200.131
- 2011-000392-14
First Posted:
May 2, 2011
Last Update Posted:
Dec 7, 2017
Last Verified:
Nov 1, 2017
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This was a randomised, placebo-controlled, double-blind, parallel arms, multinational phase III trial in which patients were randomised 2:1 to Afatinib or Placebo. |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Period Title: Overall Study | ||
| STARTED | 411 | 206 |
| COMPLETED | 124 | 87 |
| NOT COMPLETED | 287 | 119 |
Baseline Characteristics
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Total of all reporting groups |
| Overall Participants | 411 | 206 | 617 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
58.3
(8.23)
|
57.3
(8.64)
|
58.0
(8.38)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
61
14.8%
|
28
13.6%
|
89
14.4%
|
| Male |
350
85.2%
|
178
86.4%
|
528
85.6%
|
Outcome Measures
| Title | Disease Free Survival (DFS) |
|---|---|
| Description | 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. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised) |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 411 | 206 |
| Median (Inter-Quartile Range) [Months] |
43.40
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | DFS was analysed using a stratified log-rank test with nodal status (N0- N2a vs. N2b-N3) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1) being the stratification factors. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4806 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.126 | |
| Confidence Interval |
(2-Sided) 95% 0.809 to 1.569 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio (Afatinib vs. Placebo) from Cox proportional hazards model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Title | Disease Free Survival (DFS) Rate at 2 Years |
|---|---|
| Description | 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. |
| Time Frame | Up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set, the number of patients from the randomized set those are disease free (or DFS) at 2 years. |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 117 | 76 |
| Number (95% Confidence Interval) [Probability (%)] |
67.2
|
73.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Kaplan-Meier (KM) curves were calculated for each treatment group, separately, and the estimates of DFS probabilities from the curves and 95% Confidence interval (CI) (using the Greenwood standard error estimate) were tabulated | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1610 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Kaplan-Meier estimates |
| Estimated Value | -6.27 | |
| Confidence Interval |
(2-Sided) 95% -15.04 to 2.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in Kaplan-Meier estimates of Afatinib vs. Placebo is provided. | |
| Title | Percentage of Patient Deaths (Overall Survival (OS)) |
|---|---|
| Description | 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. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised) |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 411 | 206 |
| Number [Percentage of patients] |
15.1
|
11.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Hazard ratio from Cox proportional hazards model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1301 |
| Comments | p-value (two-sided) from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.444 | |
| Confidence Interval |
(2-Sided) 95% 0.895 to 2.332 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patients With Improved Health Related Quality of Life (HRQOL) |
|---|---|
| Description | 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 Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised) |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 411 | 206 |
| Swallowing (Q5-Q8 from QLQ-HN35) |
34.8
|
27.2
|
| Pain HN35 (Q1-Q4 from QLQ-HN35) |
33.8
|
26.2
|
| Global health status/QoL(Q29-Q30 from QLQ-C30) |
33.6
|
38.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Swallowing (Q5-Q8 from QLQ-HN35). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0561 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.431 | |
| Confidence Interval |
(2-Sided) 95% 0.991 to 2.068 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Pain HN35 (Q1-Q4 from QLQ-HN35). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0523 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.446 | |
| Confidence Interval |
(2-Sided) 95% 0.996 to 2.098 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Global health status/QoL(Q29-Q30 from QLQ-C30). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2570 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.818 | |
| Confidence Interval |
(2-Sided) 95% 0.577 to 1.158 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Deterioration in Health Related Quality of Life (HRQOL) |
|---|---|
| Description | 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. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised) |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 411 | 206 |
| Swallowing |
18.43
|
31.44
|
| Pain HN35 |
12.06
|
31.08
|
| Global health status/QoL |
7.59
|
25.79
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | For swallowing scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0591 |
| Comments | P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.295 | |
| Confidence Interval |
(2-Sided) 95% 0.986 to 1.700 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | For pain HN35 scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0049 |
| Comments | P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.456 | |
| Confidence Interval |
(2-Sided) 95% 1.113 to 1.905 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | For global health status/QoL scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.604 | |
| Confidence Interval |
(2-Sided) 95% 1.238 to 2.079 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Health Related Quality of Life (HRQOL) Scores Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised) |
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo |
|---|---|---|
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. |
| Measure Participants | 411 | 206 |
| Swallowing |
10.1
(1.00)
|
8.8
(1.12)
|
| Pain HN35 |
13.1
(0.98)
|
9.9
(1.10)
|
| Global health status/QoL |
29.6
(2.23)
|
33.0
(2.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Scores (swallowing scale) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2232 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Degrees of freedom calculated using the Kenward-Roger method. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% -0.81 to 3.45 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.08 |
|
| Estimation Comments | Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Scores (pain scale) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0028 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Degrees of freedom calculated using the Kenward-Roger method. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.2 | |
| Confidence Interval |
(2-Sided) 95% 1.12 to 5.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.08 |
|
| Estimation Comments | Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Afatinib (BIBW 2992), Placebo |
|---|---|---|
| Comments | Scores (global health/QoL) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Degrees of freedom calculated using the Kenward-Roger method. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -3.4 | |
| Confidence Interval |
(2-Sided) 95% -5.33 to -1.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.98 |
|
| Estimation Comments | Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3). | |
Adverse Events
| Time Frame | From first drug administration until 4 weeks after the last drug administration, up to 84 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Afatinib (BIBW 2992) | Placebo | ||
| Arm/Group Description | Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. | ||
All Cause Mortality |
||||
| Afatinib (BIBW 2992) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Afatinib (BIBW 2992) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 80/411 (19.5%) | 51/206 (24.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 4/411 (1%) | 2/206 (1%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/411 (0%) | 1/206 (0.5%) | ||
| Aortic valve stenosis | 0/411 (0%) | 1/206 (0.5%) | ||
| Arrhythmia | 0/411 (0%) | 2/206 (1%) | ||
| Atrial flutter | 1/411 (0.2%) | 0/206 (0%) | ||
| Cardiac arrest | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Cardiac failure congestive | 0/411 (0%) | 1/206 (0.5%) | ||
| Cardio-respiratory arrest | 1/411 (0.2%) | 0/206 (0%) | ||
| Ear and labyrinth disorders | ||||
| Deafness neurosensory | 1/411 (0.2%) | 0/206 (0%) | ||
| Endocrine disorders | ||||
| Inappropriate antidiuretic hormone secretion | 0/411 (0%) | 1/206 (0.5%) | ||
| Eye disorders | ||||
| Retinal tear | 1/411 (0.2%) | 0/206 (0%) | ||
| Gastrointestinal disorders | ||||
| Colitis | 0/411 (0%) | 1/206 (0.5%) | ||
| Diarrhoea | 2/411 (0.5%) | 0/206 (0%) | ||
| Duodenal ulcer haemorrhage | 1/411 (0.2%) | 0/206 (0%) | ||
| Dyspepsia | 1/411 (0.2%) | 0/206 (0%) | ||
| Dysphagia | 2/411 (0.5%) | 1/206 (0.5%) | ||
| Gastric perforation | 1/411 (0.2%) | 0/206 (0%) | ||
| Gastrointestinal haemorrhage | 1/411 (0.2%) | 0/206 (0%) | ||
| Glossitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Intestinal haemorrhage | 1/411 (0.2%) | 0/206 (0%) | ||
| Large intestine polyp | 0/411 (0%) | 1/206 (0.5%) | ||
| Melaena | 1/411 (0.2%) | 0/206 (0%) | ||
| Nausea | 1/411 (0.2%) | 0/206 (0%) | ||
| Oesophagitis | 0/411 (0%) | 1/206 (0.5%) | ||
| Pancreatitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Pancreatitis acute | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Pancreatitis relapsing | 1/411 (0.2%) | 0/206 (0%) | ||
| Stomatitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Vomiting | 1/411 (0.2%) | 0/206 (0%) | ||
| General disorders | ||||
| Asthenia | 0/411 (0%) | 1/206 (0.5%) | ||
| Death | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Disease recurrence | 1/411 (0.2%) | 0/206 (0%) | ||
| Fatigue | 0/411 (0%) | 1/206 (0.5%) | ||
| Impaired healing | 0/411 (0%) | 1/206 (0.5%) | ||
| Malaise | 1/411 (0.2%) | 0/206 (0%) | ||
| Mucosal inflammation | 1/411 (0.2%) | 0/206 (0%) | ||
| Non-cardiac chest pain | 1/411 (0.2%) | 0/206 (0%) | ||
| Oedema | 0/411 (0%) | 1/206 (0.5%) | ||
| Pyrexia | 1/411 (0.2%) | 0/206 (0%) | ||
| Sudden death | 1/411 (0.2%) | 0/206 (0%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stone | 1/411 (0.2%) | 0/206 (0%) | ||
| Cholecystitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Cholelithiasis | 1/411 (0.2%) | 0/206 (0%) | ||
| Hepatic failure | 1/411 (0.2%) | 0/206 (0%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/411 (0.2%) | 0/206 (0%) | ||
| Sarcoidosis | 0/411 (0%) | 1/206 (0.5%) | ||
| Infections and infestations | ||||
| Appendicitis perforated | 0/411 (0%) | 1/206 (0.5%) | ||
| Carbuncle | 1/411 (0.2%) | 0/206 (0%) | ||
| Cellulitis | 2/411 (0.5%) | 0/206 (0%) | ||
| Cellulitis of male external genital organ | 1/411 (0.2%) | 0/206 (0%) | ||
| Diverticulitis | 0/411 (0%) | 1/206 (0.5%) | ||
| Erysipelas | 1/411 (0.2%) | 0/206 (0%) | ||
| Groin infection | 1/411 (0.2%) | 0/206 (0%) | ||
| Hepatitis E | 0/411 (0%) | 1/206 (0.5%) | ||
| Infection | 1/411 (0.2%) | 0/206 (0%) | ||
| Lung infection | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Oropharyngeal candidiasis | 1/411 (0.2%) | 0/206 (0%) | ||
| Osteomyelitis | 0/411 (0%) | 1/206 (0.5%) | ||
| Pneumonia | 1/411 (0.2%) | 5/206 (2.4%) | ||
| Respiratory tract infection | 0/411 (0%) | 1/206 (0.5%) | ||
| Septic shock | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Upper respiratory tract infection | 1/411 (0.2%) | 0/206 (0%) | ||
| Urethritis | 1/411 (0.2%) | 0/206 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Accident | 0/411 (0%) | 1/206 (0.5%) | ||
| Accidental overdose | 1/411 (0.2%) | 0/206 (0%) | ||
| Osteoradionecrosis | 2/411 (0.5%) | 0/206 (0%) | ||
| Patella fracture | 0/411 (0%) | 1/206 (0.5%) | ||
| Post procedural complication | 0/411 (0%) | 1/206 (0.5%) | ||
| Post procedural haemorrhage | 1/411 (0.2%) | 0/206 (0%) | ||
| Radiation fibrosis | 1/411 (0.2%) | 0/206 (0%) | ||
| Radiation necrosis | 1/411 (0.2%) | 0/206 (0%) | ||
| Vascular graft complication | 0/411 (0%) | 1/206 (0.5%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 1/411 (0.2%) | 0/206 (0%) | ||
| Blood bilirubin increased | 1/411 (0.2%) | 0/206 (0%) | ||
| Electrocardiogram QT prolonged | 1/411 (0.2%) | 0/206 (0%) | ||
| Gamma-glutamyltransferase increased | 1/411 (0.2%) | 0/206 (0%) | ||
| Weight decreased | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 3/411 (0.7%) | 1/206 (0.5%) | ||
| Dehydration | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Hypokalaemia | 1/411 (0.2%) | 0/206 (0%) | ||
| Hyponatraemia | 2/411 (0.5%) | 0/206 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Groin pain | 1/411 (0.2%) | 0/206 (0%) | ||
| Neck pain | 1/411 (0.2%) | 0/206 (0%) | ||
| Osteonecrosis | 0/411 (0%) | 3/206 (1.5%) | ||
| Osteonecrosis of jaw | 0/411 (0%) | 1/206 (0.5%) | ||
| Scleroderma | 2/411 (0.5%) | 1/206 (0.5%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 3/411 (0.7%) | 0/206 (0%) | ||
| Colon cancer | 0/411 (0%) | 1/206 (0.5%) | ||
| Lung neoplasm malignant | 0/411 (0%) | 1/206 (0.5%) | ||
| Metastases to lung | 2/411 (0.5%) | 0/206 (0%) | ||
| Metastases to lymph nodes | 0/411 (0%) | 1/206 (0.5%) | ||
| Neoplasm recurrence | 5/411 (1.2%) | 3/206 (1.5%) | ||
| Oesophageal carcinoma | 0/411 (0%) | 1/206 (0.5%) | ||
| Oropharyngeal squamous cell carcinoma | 2/411 (0.5%) | 1/206 (0.5%) | ||
| Recurrent cancer | 1/411 (0.2%) | 0/206 (0%) | ||
| Squamous cell carcinoma of skin | 1/411 (0.2%) | 0/206 (0%) | ||
| Nervous system disorders | ||||
| Carotid artery thrombosis | 1/411 (0.2%) | 0/206 (0%) | ||
| Cerebrovascular accident | 2/411 (0.5%) | 0/206 (0%) | ||
| Ischaemic stroke | 1/411 (0.2%) | 1/206 (0.5%) | ||
| Migraine | 1/411 (0.2%) | 0/206 (0%) | ||
| Partial seizures with secondary generalisation | 1/411 (0.2%) | 0/206 (0%) | ||
| Presyncope | 0/411 (0%) | 1/206 (0.5%) | ||
| Sciatica | 0/411 (0%) | 1/206 (0.5%) | ||
| Spinal cord compression | 1/411 (0.2%) | 0/206 (0%) | ||
| Syncope | 0/411 (0%) | 1/206 (0.5%) | ||
| Wernicke's encephalopathy | 1/411 (0.2%) | 0/206 (0%) | ||
| Product Issues | ||||
| Device occlusion | 1/411 (0.2%) | 0/206 (0%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/411 (0.5%) | 0/206 (0%) | ||
| Renal failure | 1/411 (0.2%) | 0/206 (0%) | ||
| Renal impairment | 1/411 (0.2%) | 0/206 (0%) | ||
| Urinary retention | 0/411 (0%) | 1/206 (0.5%) | ||
| Reproductive system and breast disorders | ||||
| Balanoposthitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Aspiration | 1/411 (0.2%) | 0/206 (0%) | ||
| Cough | 0/411 (0%) | 1/206 (0.5%) | ||
| Dyspnoea | 2/411 (0.5%) | 3/206 (1.5%) | ||
| Interstitial lung disease | 3/411 (0.7%) | 0/206 (0%) | ||
| Laryngeal dyspnoea | 0/411 (0%) | 1/206 (0.5%) | ||
| Laryngeal oedema | 8/411 (1.9%) | 8/206 (3.9%) | ||
| Laryngeal stenosis | 1/411 (0.2%) | 0/206 (0%) | ||
| Pneumonitis | 1/411 (0.2%) | 0/206 (0%) | ||
| Pneumothorax | 2/411 (0.5%) | 0/206 (0%) | ||
| Pneumothorax spontaneous | 0/411 (0%) | 1/206 (0.5%) | ||
| Pulmonary alveolar haemorrhage | 0/411 (0%) | 1/206 (0.5%) | ||
| Pulmonary hypertension | 1/411 (0.2%) | 0/206 (0%) | ||
| Respiratory arrest | 1/411 (0.2%) | 0/206 (0%) | ||
| Respiratory failure | 1/411 (0.2%) | 0/206 (0%) | ||
| Respiratory tract oedema | 1/411 (0.2%) | 0/206 (0%) | ||
| Tracheal stenosis | 0/411 (0%) | 1/206 (0.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis exfoliative | 1/411 (0.2%) | 0/206 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/411 (0.2%) | 0/206 (0%) | ||
| Hypotension | 0/411 (0%) | 1/206 (0.5%) | ||
| Peripheral ischaemia | 1/411 (0.2%) | 1/206 (0.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Afatinib (BIBW 2992) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 407/411 (99%) | 169/206 (82%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 23/411 (5.6%) | 7/206 (3.4%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 21/411 (5.1%) | 6/206 (2.9%) | ||
| Cheilitis | 22/411 (5.4%) | 1/206 (0.5%) | ||
| Constipation | 33/411 (8%) | 20/206 (9.7%) | ||
| Diarrhoea | 335/411 (81.5%) | 41/206 (19.9%) | ||
| Dry mouth | 55/411 (13.4%) | 25/206 (12.1%) | ||
| Dyspepsia | 42/411 (10.2%) | 10/206 (4.9%) | ||
| Dysphagia | 48/411 (11.7%) | 21/206 (10.2%) | ||
| Gastrooesophageal reflux disease | 23/411 (5.6%) | 2/206 (1%) | ||
| Nausea | 43/411 (10.5%) | 24/206 (11.7%) | ||
| Oral pain | 23/411 (5.6%) | 6/206 (2.9%) | ||
| Stomatitis | 107/411 (26%) | 12/206 (5.8%) | ||
| Vomiting | 40/411 (9.7%) | 20/206 (9.7%) | ||
| General disorders | ||||
| Asthenia | 43/411 (10.5%) | 23/206 (11.2%) | ||
| Fatigue | 61/411 (14.8%) | 21/206 (10.2%) | ||
| Mucosal inflammation | 126/411 (30.7%) | 17/206 (8.3%) | ||
| Pyrexia | 29/411 (7.1%) | 7/206 (3.4%) | ||
| Infections and infestations | ||||
| Conjunctivitis | 21/411 (5.1%) | 2/206 (1%) | ||
| Nasopharyngitis | 22/411 (5.4%) | 18/206 (8.7%) | ||
| Paronychia | 85/411 (20.7%) | 4/206 (1.9%) | ||
| Upper respiratory tract infection | 19/411 (4.6%) | 15/206 (7.3%) | ||
| Investigations | ||||
| Weight decreased | 67/411 (16.3%) | 19/206 (9.2%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 74/411 (18%) | 23/206 (11.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 13/411 (3.2%) | 17/206 (8.3%) | ||
| Muscle spasms | 26/411 (6.3%) | 9/206 (4.4%) | ||
| Neck pain | 11/411 (2.7%) | 11/206 (5.3%) | ||
| Nervous system disorders | ||||
| Dizziness | 11/411 (2.7%) | 13/206 (6.3%) | ||
| Dysgeusia | 34/411 (8.3%) | 10/206 (4.9%) | ||
| Headache | 18/411 (4.4%) | 12/206 (5.8%) | ||
| Psychiatric disorders | ||||
| Anxiety | 10/411 (2.4%) | 12/206 (5.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 35/411 (8.5%) | 30/206 (14.6%) | ||
| Dysphonia | 22/411 (5.4%) | 17/206 (8.3%) | ||
| Epistaxis | 54/411 (13.1%) | 3/206 (1.5%) | ||
| Oropharyngeal pain | 27/411 (6.6%) | 14/206 (6.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne | 22/411 (5.4%) | 2/206 (1%) | ||
| Dermatitis acneiform | 112/411 (27.3%) | 6/206 (2.9%) | ||
| Dry skin | 76/411 (18.5%) | 16/206 (7.8%) | ||
| Erythema | 28/411 (6.8%) | 5/206 (2.4%) | ||
| Palmar-plantar erythrodysaesthesia syndrome | 30/411 (7.3%) | 0/206 (0%) | ||
| Pruritus | 58/411 (14.1%) | 13/206 (6.3%) | ||
| Rash | 188/411 (45.7%) | 34/206 (16.5%) | ||
| Skin fissures | 40/411 (9.7%) | 1/206 (0.5%) | ||
| Vascular disorders | ||||
| Hypertension | 18/411 (4.4%) | 12/206 (5.8%) | ||
Limitations/Caveats
The trial was stopped prematurely due to futility.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
| Name/Title | Boehringer Ingelheim, Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01345669
Other Study ID Numbers:
- 1200.131
- 2011-000392-14
First Posted:
May 2, 2011
Last Update Posted:
Dec 7, 2017
Last Verified:
Nov 1, 2017