Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000391-34 | EudraCT Number | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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Not provided
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
Not provided
Not provided
Not provided
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Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afatinib (BIBW 2992) | Experimental | Once daily |
|
| Methotrexate | Active Comparator | Weekly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afatinib | Drug | Once daily |
| |
| Methotrexate |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) Based on Central Independent Review | PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016). The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied:
| From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive. | From randomization until death or study completion date (06Dec2016); Up to 60 months |
Not provided
Inclusion criteria:
Exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.43.00113 Boehringer Ingelheim Investigational Site | Harvey | Illinois | United States | |||
| 1200.43.00106 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28961833 | Derived | Cohen EEW, Licitra LF, Burtness B, Fayette J, Gauler T, Clement PM, Grau JJ, Del Campo JM, Mailliez A, Haddad RI, Vermorken JB, Tahara M, Guigay J, Geoffrois L, Merlano MC, Dupuis N, Kramer N, Cong XJ, Gibson N, Solca F, Ehrnrooth E, Machiels JH. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer. Ann Oncol. 2017 Oct 1;28(10):2526-2532. doi: 10.1093/annonc/mdx344. | |
| 27084954 |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Afatinib (BIBW 2992) | Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
Weekly |
|
| Objective Response (OR) | OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:-
All the above scenarios should also satisfy 'No occurrence of new lesions'. | Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| Disease Control (DC) | DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:-
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 imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| Tumour Shrinkage | Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis. Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase. Percentage of Participants with Tumour shrinkage as per the categories (>=20% increase, >=0 - <20% increase, >0 - <30% decrease, >=30 - <50% decrease, >=50% decrease) are presented. | Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Status Change in Pain Scale | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Status Change in Swallowing Scale | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Status Change in Global Health Status Scale | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Time to Deterioration in Pain | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Time to Deterioration in Swallowing | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Time to Deterioration in Global Health Status | 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. | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| Peoria |
| Illinois |
| United States |
| 1200.43.00110 Boehringer Ingelheim Investigational Site | Boston | Massachusetts | United States |
| 1200.43.00107 Boehringer Ingelheim Investigational Site | Omaha | Nebraska | United States |
| 1200.43.00105 Boehringer Ingelheim Investigational Site | Stony Brook | New York | United States |
| 1200.43.00102 Boehringer Ingelheim Investigational Site | Philadelphia | Pennsylvania | United States |
| 1200.43.00103 Boehringer Ingelheim Investigational Site | Philadelphia | Pennsylvania | United States |
| 1200.43.00109 Boehringer Ingelheim Investigational Site | San Antonio | Texas | United States |
| 1200.43.05401 Boehringer Ingelheim Investigational Site | Ciudad Autonoma de Bs As | Argentina |
| 1200.43.05402 Boehringer Ingelheim Investigational Site | Santa Fe | Argentina |
| 1200.43.05403 Boehringer Ingelheim Investigational Site | Villa DomÃnico | Argentina |
| 1200.43.04303 Boehringer Ingelheim Investigational Site | Leoben | Austria |
| 1200.43.04305 Boehringer Ingelheim Investigational Site | Salzburg | Austria |
| 1200.43.04301 Boehringer Ingelheim Investigational Site | Vienna | Austria |
| 1200.43.03202 Boehringer Ingelheim Investigational Site | Brussels | Belgium |
| 1200.43.03203 Boehringer Ingelheim Investigational Site | Edegem | Belgium |
| 1200.43.03204 Boehringer Ingelheim Investigational Site | Ghent | Belgium |
| 1200.43.03201 Boehringer Ingelheim Investigational Site | Leuven | Belgium |
| 1200.43.05504 Boehringer Ingelheim Investigational Site | Barretos | Brazil |
| 1200.43.05505 Boehringer Ingelheim Investigational Site | Jaú | Brazil |
| 1200.43.05507 Boehringer Ingelheim Investigational Site | Passo Fundo | Brazil |
| 1200.43.05503 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1200.43.05502 Boehringer Ingelheim Investigational Site | Rio de Janeiro | Brazil |
| 1200.43.05501 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 1200.43.05506 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 1200.43.04202 Boehringer Ingelheim Investigational Site | Olomouc | Czechia |
| 1200.43.04201 Boehringer Ingelheim Investigational Site | Prague | Czechia |
| 1200.43.04203 Boehringer Ingelheim Investigational Site | Prague | Czechia |
| 1200.43.04501 Boehringer Ingelheim Investigational Site | København Ø | Denmark |
| 1200.43.03304 Boehringer Ingelheim Investigational Site | Avignon | France |
| 1200.43.03306 Boehringer Ingelheim Investigational Site | Clermont-Ferrand | 63011 | France |
| 1200.43.03312 Boehringer Ingelheim Investigational Site | Dijon | France |
| 1200.43.03303 Boehringer Ingelheim Investigational Site | Lille | France |
| 1200.43.03301 Boehringer Ingelheim Investigational Site | Lyon | France |
| 1200.43.03302 Boehringer Ingelheim Investigational Site | Montpellier | France |
| 1200.43.03307 Boehringer Ingelheim Investigational Site | Nice | France |
| 1200.43.03314 Boehringer Ingelheim Investigational Site | Paris | France |
| 1200.43.03305 Boehringer Ingelheim Investigational Site | Poitiers | France |
| 1200.43.03316 Boehringer Ingelheim Investigational Site | Rouen | France |
| 1200.43.03309 Boehringer Ingelheim Investigational Site | Saint-Herblain | France |
| 1200.43.03310 Boehringer Ingelheim Investigational Site | Vandœuvre-lès-Nancy | France |
| 1200.43.03317 Boehringer Ingelheim Investigational Site | Villejuif | France |
| 1200.43.04903 Boehringer Ingelheim Investigational Site | Aachen | Germany |
| 1200.43.04902 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1200.43.04909 Boehringer Ingelheim Investigational Site | Dresden | Germany |
| 1200.43.04901 Boehringer Ingelheim Investigational Site | Essen | Germany |
| 1200.43.04905 Boehringer Ingelheim Investigational Site | Hamburg | Germany |
| 1200.43.04906 Boehringer Ingelheim Investigational Site | Hanover | Germany |
| 1200.43.04908 Boehringer Ingelheim Investigational Site | Jena | Germany |
| 1200.43.04904 Boehringer Ingelheim Investigational Site | Leipzig | Germany |
| 1200.43.04907 Boehringer Ingelheim Investigational Site | Mannheim | Germany |
| 1200.43.03004 Boehringer Ingelheim Investigational Site | Haidari | Greece |
| 1200.43.03005 Boehringer Ingelheim Investigational Site | Heraklion | Greece |
| 1200.43.03002 Boehringer Ingelheim Investigational Site | Thessaloniki | Greece |
| 1200.43.97201 Boehringer Ingelheim Investigational Site | Haifa | Israel |
| 1200.43.97203 Boehringer Ingelheim Investigational Site | Petah Tikva | Israel |
| 1200.43.97204 Boehringer Ingelheim Investigational Site | Tel Litwinsky | Israel |
| 1200.43.03909 Boehringer Ingelheim Investigational Site | Aosta | Italy |
| 1200.43.03908 Boehringer Ingelheim Investigational Site | Cagliari | Italy |
| 1200.43.03901 Boehringer Ingelheim Investigational Site | Confreria (CN) | Italy |
| 1200.43.03907 Boehringer Ingelheim Investigational Site | Milan | Italy |
| 1200.43.03903 Boehringer Ingelheim Investigational Site | Naples | Italy |
| 1200.43.03905 Boehringer Ingelheim Investigational Site | Palermo | Italy |
| 1200.43.03902 Boehringer Ingelheim Investigational Site | Savona | Italy |
| 1200.43.03904 Boehringer Ingelheim Investigational Site | Taormina (ME) | Italy |
| 1200.43.03906 Boehringer Ingelheim Investigational Site | Venezia | Italy |
| 1200.43.03910 Boehringer Ingelheim Investigational Site | Viterbo | Italy |
| 1200.43.08106 Boehringer Ingelheim Investigational Site | Aichi, Nagoya | Japan |
| 1200.43.08103 Boehringer Ingelheim Investigational Site | Chiba, Kashiwa | Japan |
| 1200.43.08108 Boehringer Ingelheim Investigational Site | Ehime, Matsuyama | Japan |
| 1200.43.08111 Boehringer Ingelheim Investigational Site | Hyogo, Akashi | Japan |
| 1200.43.08107 Boehringer Ingelheim Investigational Site | Hyogo, Kobe | Japan |
| 1200.43.08109 Boehringer Ingelheim Investigational Site | Kanagawa, Isehara | Japan |
| 1200.43.08114 Boehringer Ingelheim Investigational Site | Miyagi, Natori | Japan |
| 1200.43.08110 Boehringer Ingelheim Investigational Site | Osaka, Osaka | Japan |
| 1200.43.08105 Boehringer Ingelheim Investigational Site | Shizuoka, Sunto-gun | Japan |
| 1200.43.08102 Boehringer Ingelheim Investigational Site | Tochigi, Shimotsuke | Japan |
| 1200.43.08113 Boehringer Ingelheim Investigational Site | Tokyo, Koto-ku | Japan |
| 1200.43.08104 Boehringer Ingelheim Investigational Site | Tokyo, Meguro-ku | Japan |
| 1200.43.08112 Boehringer Ingelheim Investigational Site | Tokyo, Minato-ku | Japan |
| 1200.43.05202 Boehringer Ingelheim Investigational Site | México | Mexico |
| 1200.43.00704 Boehringer Ingelheim Investigational Site | Ivanovo | Russia |
| 1200.43.00706 Boehringer Ingelheim Investigational Site | Kurski | Russia |
| 1200.43.00709 Boehringer Ingelheim Investigational Site | Moscow | Russia |
| 1200.43.00703 Boehringer Ingelheim Investigational Site | Omsk | Russia |
| 1200.43.00710 Boehringer Ingelheim Investigational Site | Pyatigorsk | Russia |
| 1200.43.00707 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russia |
| 1200.43.00705 Boehringer Ingelheim Investigational Site | Ufa | Russia |
| 1200.43.02703 Boehringer Ingelheim Investigational Site | Cape Town | South Africa |
| 1200.43.02704 Boehringer Ingelheim Investigational Site | Kraaifontein, Cape Town | South Africa |
| 1200.43.02701 Boehringer Ingelheim Investigational Site | Parktown, Johannesburg | South Africa |
| 1200.43.02702 Boehringer Ingelheim Investigational Site | Pretoria | South Africa |
| 1200.43.03401 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1200.43.03404 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1200.43.03405 Boehringer Ingelheim Investigational Site | Girona | Spain |
| 1200.43.03406 Boehringer Ingelheim Investigational Site | Málaga | Spain |
| 1200.43.03402 Boehringer Ingelheim Investigational Site | Salamanca | Spain |
| 1200.43.03403 Boehringer Ingelheim Investigational Site | Zaragoza | Spain |
| 1200.43.04602 Boehringer Ingelheim Investigational Site | Gothenburg | Sweden |
| 1200.43.04101 Boehringer Ingelheim Investigational Site | Basel | 4031 | Switzerland |
| 1200.43.04102 Boehringer Ingelheim Investigational Site | Bern | Switzerland |
| Derived |
| Clement PM, Gauler T, Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Cohen EE, 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, Vermorken JB; LUX-H&N 1 investigators. Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial. Ann Oncol. 2016 Aug;27(8):1585-93. doi: 10.1093/annonc/mdw151. Epub 2016 Apr 15. |
| 25892145 | Derived | 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. Epub 2015 Apr 16. |
| FG001 |
| Methotrexate |
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
The randomised set (RS) included all patients who were randomised to receive treatment, whether treated or not
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Afatinib (BIBW 2992) | Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
| BG001 | Methotrexate | Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-free Survival (PFS) Based on Central Independent Review | PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016). The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied:
| Randomised set (RS) | Posted | Median | 95% Confidence Interval | months | From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive. | RS | Posted | Median | 95% Confidence Interval | months | From randomization until death or study completion date (06Dec2016); Up to 60 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Objective Response (OR) | OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:-
All the above scenarios should also satisfy 'No occurrence of new lesions'. | RS | Posted | Number | 95% Confidence Interval | percentage of participants | Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Disease Control (DC) | DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:-
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. | RS | Posted | Number | 95% Confidence Interval | percentage of participants | Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Tumour Shrinkage | Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis. Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase. Percentage of Participants with Tumour shrinkage as per the categories (>=20% increase, >=0 - <20% increase, >0 - <30% decrease, >=30 - <50% decrease, >=50% decrease) are presented. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Number | percentage of participants | Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Mean | Standard Error | scores on a scale | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Mean | Standard Error | scores on a scale | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time | The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome. Changes in scores over time were assessed using longitudinal models. The analyses of HRQOL are presented for the 07 May 2014 cut-off date. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Mean | Standard Error | scores on a scale | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Status Change in Pain Scale | 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. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Number | percentage of participants | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Status Change in Swallowing Scale | 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. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Number | percentage of participants | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Status Change in Global Health Status Scale | 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. | RS (Only patients with observed cases (OC) values were analysed) | Posted | Number | percentage of participants | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Deterioration in Pain | 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. | RS | Posted | Median | 95% Confidence Interval | months | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Deterioration in Swallowing | 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. | RS | Posted | Median | 95% Confidence Interval | months | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Deterioration in Global Health Status | 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. | RS | Posted | Median | 95% Confidence Interval | months | From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months. |
|
From first administration of study medication (afatinib or methotrexate) and within 28 days after the last administration of study medication (study completion date is 06Dec2016); Up to 60 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afatinib (BIBW 2992) | Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. | 168 | 320 | 309 | 320 | ||
| EG001 | Methotrexate | Intravenous bolus injection of Methotrexate Starting dose 40 milligram per square meter mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. | 73 | 160 | 146 | 160 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Atrial tachycardia | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Tracheo-oesophageal fistula | Congenital, familial and genetic disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Blindness unilateral | Eye disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Duodenal ulcer | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oesophageal fistula | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Retroperitoneal haemorrhage | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Complication associated with device | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Facial pain | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperpyrexia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Mucosal haemorrhage | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abscess oral | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Klebsiella sepsis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Oral infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tracheitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tracheobronchitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Wound sepsis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Foreign body aspiration | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Poisoning deliberate | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Tracheal haemorrhage | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Tracheal obstruction | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Vascular pseudoaneurysm | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Blood pressure orthostatic decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| False positive investigation result | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Food aversion | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fistula | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Infected neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Laryngeal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Oesophageal squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Tumour ulceration | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Paralysis recurrent laryngeal nerve | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Device dislocation | Product Issues | MedDRA 19.1 | Systematic Assessment |
| |
| Device leakage | Product Issues | MedDRA 19.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Prostatomegaly | Reproductive system and breast disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Bronchopneumopathy | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Laryngeal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Organising pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pharyngeal stenosis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary artery thrombosis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory acidosis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Respiratory tract haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Skin haemorrhage | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gastrostomy | Surgical and medical procedures | MedDRA 19.1 | Systematic Assessment |
| |
| Angiopathy | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Shock haemorrhagic | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Superior vena cava syndrome | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D002294 | Carcinoma, Squamous Cell |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077716 | Afatinib |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
Not provided
Not provided
| Male |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
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|
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
|
|
|
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
|
|
|
|
|
| OG001 | Methotrexate | Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
|
|
|
| OG001 | Methotrexate | Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
|
|
|
| OG001 | Methotrexate | Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. |
|
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| Participants |
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| Participants |
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