Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01441596
Collaborator
(none)
121
40
3
34
3
0.1
Study Details
Study Description
Brief Summary
The aim of this study is to investigate the efficacy and safety of afatinib alone or in combination with vinorelbine, as treatment in patients with HER2-overexpressing metastatic breast cancer, who have progressive brain lesions after trastuzumab and/or lapatinib based therapy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
121 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Lux-Breast 3; Randomised Phase II Study of Afatinib Alone or in Combination With Vinorelbine Versus Investigator's Choice of Treatment in Patients With HER2 Positive Breast Cancer With Progressive Brain Metastases After Trastuzumab and/or Lapatinib Based Therapy
Study Start Date
:
Oct 1, 2011
Actual Primary Completion Date
:
Feb 1, 2014
Actual Study Completion Date
:
Aug 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: arm A: Afatinib monotherapy Afatinib monotherapy: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. |
Drug: afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
|
| Experimental: arm B: Afatinib in combination with vino Afatinib 40 mg per day, continuous treatment, in combination with vinorelbine Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course. |
Drug: Vinorelbine
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
Drug: afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
|
| Active Comparator: arm C: investigator's choice of treatmen Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. |
Drug: Investigator's choice of treatment
Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines.
|
Outcome Measures
Primary Outcome Measures
- Patient Benefit Rate at 12 Weeks [12 weeks from randomisation]
Percentage of patients with patient benefit at week 12. Patient benefit was defined by the absence of central nervous system (CNS) disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in addition to no tumour-related worsening of the neurological signs and symptoms (NSS), no tumour-related increase in corticosteroid dosage and no progression of extra CNS disease according to RECIST 1.1
Secondary Outcome Measures
- Progression-Free Survival [From first drug administration until 28 days after end of treatment, up to 805 days]
Progression-Free Survival is defined as the time from the date of randomisation to the date of disease progression or death whichever came first. Disease progression was defined as either disease progression in CNS lesions (including worsening in NSS and use of corticosteroid) or disease progression in extra-CNS lesions according to RECIST 1.1.
- Overall Survival [From first drug administration until 28 days after end of treatment, up to 805 days]
Overall Survival is defined as time from randomisation to the date of death from any cause.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
patients with HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab and/or Lapatinib) based therapy (no leptomeningeal carcinomatosis as the only site of CNS metastases)
-
at least one measurable and progressive lesion in the brain (=10 mm on T1-weighted, gadolinium-enhanced Magnetic Resonance Imaging). Measurable or non measurable extracranial metastases allowed.
-
previous treatment with HER2 inhibitors to be discontinued prior to first study treatment administration (at least 14 days for trastuzumab and other antibodies, at least 7 days for lapatinib).
-
previous chemotherapy and hormonal therapy (adjuvant and metastatic regimens) allowed, but chemotherapy must have been discontinued at least 14 days and hormonal therapy at least 7 days prior to first study treatment administration.
-
Patients must have recovered to baseline condition or to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade = 1 from any acute CTCAE v. 3.0 grade =2 side effects of previous treatments.
-
prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed provided that there is unequivocal evidence of one or more new and/or progressive brain metastases after completion of whole brain radiotherapy or stereotactic radiosurgery.
Exclusion criteria:
-
Prior treatment with HER2- tyrosine kinase inhibitor other than lapatinib
-
Any other current malignancy or malignancy diagnosed within the past five (5) years (other than bilateral primary breast cancer, metastases to the contralateral breast, non-melanomatous skin cancer and in situ cervical cancer).
-
Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or Common Terminology Criteria (CTC) grade =2 diarrhoea of any aetiology.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1200.67.10106 Boehringer Ingelheim Investigational Site | Bakersfield | California | United States | |
| 2 | 1200.67.10105 Boehringer Ingelheim Investigational Site | Fullerton | California | United States | |
| 3 | 1200.67.10001 Boehringer Ingelheim Investigational Site | Los Angeles | California | United States | |
| 4 | 1200.67.10108 Boehringer Ingelheim Investigational Site | Santa Barbara | California | United States | |
| 5 | 1200.67.10003 Boehringer Ingelheim Investigational Site | Lake Success | New York | United States | |
| 6 | 1200.67.10004 Boehringer Ingelheim Investigational Site | Columbus | Ohio | United States | |
| 7 | 1200.67.11004 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada | |
| 8 | 1200.67.11003 Boehringer Ingelheim Investigational Site | Greenfield Park | Quebec | Canada | |
| 9 | 1200.67.11002 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 10 | 1200.67.35801 Boehringer Ingelheim Investigational Site | Helsinki | Finland | ||
| 11 | 1200.67.35802 Boehringer Ingelheim Investigational Site | Tampere | Finland | ||
| 12 | 1200.67.35803 Boehringer Ingelheim Investigational Site | Turku | Finland | ||
| 13 | 1200.67.33009 Boehringer Ingelheim Investigational Site | Caen Cedex | France | ||
| 14 | 1200.67.33010 Boehringer Ingelheim Investigational Site | Clermont-Ferrand cedex 1 | France | ||
| 15 | 1200.67.33008 Boehringer Ingelheim Investigational Site | Lille Cedex | France | ||
| 16 | 1200.67.33001 Boehringer Ingelheim Investigational Site | Lyon Cedex 08 | France | ||
| 17 | 1200.67.33004 Boehringer Ingelheim Investigational Site | Marseille Cedex 09 | France | ||
| 18 | 1200.67.33011 Boehringer Ingelheim Investigational Site | Nice Cedex 02 | France | ||
| 19 | 1200.67.33002 Boehringer Ingelheim Investigational Site | Paris Cedex 05 | France | ||
| 20 | 1200.67.33003 Boehringer Ingelheim Investigational Site | Paris | France | ||
| 21 | 1200.67.33012 Boehringer Ingelheim Investigational Site | Saint Cloud | France | ||
| 22 | 1200.67.33005 Boehringer Ingelheim Investigational Site | Saint Herblain Cedex | France | ||
| 23 | 1200.67.49002 Boehringer Ingelheim Investigational Site | Erlangen | Germany | ||
| 24 | 1200.67.49008 Boehringer Ingelheim Investigational Site | Essen | Germany | ||
| 25 | 1200.67.49005 Boehringer Ingelheim Investigational Site | Hannover | Germany | ||
| 26 | 1200.67.49006 Boehringer Ingelheim Investigational Site | Heidelberg | Germany | ||
| 27 | 1200.67.49007 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 28 | 1200.67.49003 Boehringer Ingelheim Investigational Site | Oldenburg | Germany | ||
| 29 | 1200.67.49004 Boehringer Ingelheim Investigational Site | Tübingen | Germany | ||
| 30 | 1200.67.39001 Boehringer Ingelheim Investigational Site | Modena | Italy | ||
| 31 | 1200.67.39002 Boehringer Ingelheim Investigational Site | Reggio Emilia | Italy | ||
| 32 | 1200.67.82001 Boehringer Ingelheim Investigational Site | Goyang | Korea, Republic of | ||
| 33 | 1200.67.82002 Boehringer Ingelheim Investigational Site | Seoul | Korea, Republic of | ||
| 34 | 1200.67.82003 Boehringer Ingelheim Investigational Site | Seoul | Korea, Republic of | ||
| 35 | 1200.67.82004 Boehringer Ingelheim Investigational Site | Seoul | Korea, Republic of | ||
| 36 | 1200.67.34002 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 37 | 1200.67.34006 Boehringer Ingelheim Investigational Site | Córdoba | Spain | ||
| 38 | 1200.67.34005 Boehringer Ingelheim Investigational Site | L'Hospitalet de Llobregat | Spain | ||
| 39 | 1200.67.34003 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 40 | 1200.67.34004 Boehringer Ingelheim Investigational Site | Valencia | Spain |
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:
NCT01441596
Other Study ID Numbers:
- 1200.67
- 2010-021415-16
First Posted:
Sep 27, 2011
Last Update Posted:
Sep 7, 2015
Last Verified:
Aug 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice |
|---|---|---|---|
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. |
| Period Title: Overall Study | |||
| STARTED | 40 | 38 | 43 |
| COMPLETED | 36 | 35 | 39 |
| NOT COMPLETED | 4 | 3 | 4 |
Baseline Characteristics
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice | Total |
|---|---|---|---|---|
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. | Total of all reporting groups |
| Overall Participants | 40 | 38 | 43 | 121 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
51.5
(10.3)
|
51.2
(10.6)
|
52.6
(10.3)
|
51.8
(10.3)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
40
100%
|
38
100%
|
43
100%
|
121
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Patient Benefit Rate at 12 Weeks |
|---|---|
| Description | Percentage of patients with patient benefit at week 12. Patient benefit was defined by the absence of central nervous system (CNS) disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in addition to no tumour-related worsening of the neurological signs and symptoms (NSS), no tumour-related increase in corticosteroid dosage and no progression of extra CNS disease according to RECIST 1.1 |
| Time Frame | 12 weeks from randomisation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomised Set (RS): includes all randomised patients, whether treated or not. |
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice |
|---|---|---|---|
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. |
| Measure Participants | 40 | 38 | 43 |
| Number (95% Confidence Interval) [percentage of participants] |
30.0
75%
|
34.2
90%
|
41.9
97.4%
|
| Title | Progression-Free Survival |
|---|---|
| Description | Progression-Free Survival is defined as the time from the date of randomisation to the date of disease progression or death whichever came first. Disease progression was defined as either disease progression in CNS lesions (including worsening in NSS and use of corticosteroid) or disease progression in extra-CNS lesions according to RECIST 1.1. |
| Time Frame | From first drug administration until 28 days after end of treatment, up to 805 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| RS including only patients who experienced disease progression or death |
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice |
|---|---|---|---|
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. |
| Measure Participants | 40 | 38 | 43 |
| Median (Inter-Quartile Range) [weeks] |
11.9
|
12.3
|
18.4
|
| Title | Overall Survival |
|---|---|
| Description | Overall Survival is defined as time from randomisation to the date of death from any cause. |
| Time Frame | From first drug administration until 28 days after end of treatment, up to 805 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| RS including only patients who died |
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice |
|---|---|---|---|
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. |
| Measure Participants | 40 | 38 | 43 |
| Median (Inter-Quartile Range) [weeks] |
57.7
|
37.3
|
52.1
|
Adverse Events
| Time Frame | From first drug administration until 28 days after end of treatment, up to 805 days | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Afatinib Mono | Afatinib+Vino | Investigator's Choice | |||
| Arm/Group Description | Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Afatinib 40 mg per day administered orally, continuous treatment, in combination with weekly Vinorelbine 25 mg/m² administered intravenously on days 1, 8, 15 in a 3-weekly course. | Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines. | |||
All Cause Mortality |
||||||
| Afatinib Mono | Afatinib+Vino | Investigator's Choice | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Afatinib Mono | Afatinib+Vino | Investigator's Choice | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/40 (45%) | 24/37 (64.9%) | 22/42 (52.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Febrile neutropenia | 0/40 (0%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Congenital, familial and genetic disorders | ||||||
| Progressive cerebellar degeneration | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 3/40 (7.5%) | 5/37 (13.5%) | 1/42 (2.4%) | |||
| Dysphagia | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Enteritis | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Ileus | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Intestinal obstruction | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Nausea | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Stomatitis | 1/40 (2.5%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Subileus | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Vomiting | 3/40 (7.5%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| General disorders | ||||||
| Asthenia | 0/40 (0%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| Chest discomfort | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Concomitant disease progression | 0/40 (0%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Death | 0/40 (0%) | 0/37 (0%) | 2/42 (4.8%) | |||
| General physical health deterioration | 4/40 (10%) | 6/37 (16.2%) | 1/42 (2.4%) | |||
| Generalised oedema | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Mucosal inflammation | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Pyrexia | 1/40 (2.5%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Infections and infestations | ||||||
| Device related infection | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Erysipelas | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Infection | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Lung infection | 1/40 (2.5%) | 3/37 (8.1%) | 0/42 (0%) | |||
| Pneumonia | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Pyelonephritis acute | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Sepsis | 0/40 (0%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Septic shock | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Urinary tract infection | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Urosepsis | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Brain herniation | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Fall | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Femoral neck fracture | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Hip fracture | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Pelvic fracture | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Procedural complication | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Investigations | ||||||
| CSF protein increased | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Dehydration | 1/40 (2.5%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Hypocalcaemia | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Hypokalaemia | 1/40 (2.5%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Hypercreatinaemia | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Pain in extremity | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Spinal pain | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Malignant neoplasm progression | 1/40 (2.5%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Metastases to liver | 1/40 (2.5%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Metastases to meninges | 0/40 (0%) | 0/37 (0%) | 2/42 (4.8%) | |||
| Metastatic neoplasm | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Neoplasm progression | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Nervous system disorders | ||||||
| Carotid artery stenosis | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Cognitive disorder | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Convulsion | 2/40 (5%) | 3/37 (8.1%) | 3/42 (7.1%) | |||
| Dizziness | 1/40 (2.5%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| Epilepsy | 2/40 (5%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Headache | 0/40 (0%) | 3/37 (8.1%) | 2/42 (4.8%) | |||
| Hemiparesis | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Hemiplegia | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Loss of consciousness | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Motor dysfunction | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Motor neurone disease | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Neurological symptom | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Partial seizures | 1/40 (2.5%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Presyncope | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Somnolence | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Syncope | 1/40 (2.5%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Tremor | 1/40 (2.5%) | 0/37 (0%) | 0/42 (0%) | |||
| Psychiatric disorders | ||||||
| Confusional state | 0/40 (0%) | 0/37 (0%) | 2/42 (4.8%) | |||
| Mood altered | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 1/40 (2.5%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleural effusion | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Pneumothorax | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Respiratory distress | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/40 (0%) | 1/37 (2.7%) | 0/42 (0%) | |||
| Vascular disorders | ||||||
| Orthostatic hypotension | 0/40 (0%) | 0/37 (0%) | 1/42 (2.4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Afatinib Mono | Afatinib+Vino | Investigator's Choice | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 39/40 (97.5%) | 37/37 (100%) | 40/42 (95.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/40 (2.5%) | 12/37 (32.4%) | 6/42 (14.3%) | |||
| Leukopenia | 0/40 (0%) | 3/37 (8.1%) | 5/42 (11.9%) | |||
| Lymphopenia | 1/40 (2.5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Neutropenia | 0/40 (0%) | 23/37 (62.2%) | 11/42 (26.2%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/40 (2.5%) | 6/37 (16.2%) | 9/42 (21.4%) | |||
| Eye disorders | ||||||
| Diplopia | 0/40 (0%) | 0/37 (0%) | 5/42 (11.9%) | |||
| Dry eye | 1/40 (2.5%) | 4/37 (10.8%) | 3/42 (7.1%) | |||
| Vision blurred | 3/40 (7.5%) | 4/37 (10.8%) | 4/42 (9.5%) | |||
| Visual impairment | 3/40 (7.5%) | 5/37 (13.5%) | 5/42 (11.9%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distension | 2/40 (5%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Abdominal pain | 2/40 (5%) | 6/37 (16.2%) | 7/42 (16.7%) | |||
| Abdominal pain upper | 3/40 (7.5%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| Constipation | 8/40 (20%) | 10/37 (27%) | 14/42 (33.3%) | |||
| Diarrhoea | 36/40 (90%) | 31/37 (83.8%) | 16/42 (38.1%) | |||
| Dry mouth | 2/40 (5%) | 4/37 (10.8%) | 0/42 (0%) | |||
| Dyspepsia | 5/40 (12.5%) | 2/37 (5.4%) | 2/42 (4.8%) | |||
| Gastritis | 0/40 (0%) | 3/37 (8.1%) | 0/42 (0%) | |||
| Haemorrhoids | 4/40 (10%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Nausea | 10/40 (25%) | 13/37 (35.1%) | 15/42 (35.7%) | |||
| Stomatitis | 5/40 (12.5%) | 13/37 (35.1%) | 6/42 (14.3%) | |||
| Vomiting | 7/40 (17.5%) | 9/37 (24.3%) | 11/42 (26.2%) | |||
| General disorders | ||||||
| Asthenia | 11/40 (27.5%) | 9/37 (24.3%) | 14/42 (33.3%) | |||
| Fatigue | 8/40 (20%) | 11/37 (29.7%) | 3/42 (7.1%) | |||
| Gait disturbance | 2/40 (5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Malaise | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Mucosal inflammation | 8/40 (20%) | 11/37 (29.7%) | 6/42 (14.3%) | |||
| Oedema peripheral | 4/40 (10%) | 2/37 (5.4%) | 5/42 (11.9%) | |||
| Pain | 1/40 (2.5%) | 3/37 (8.1%) | 2/42 (4.8%) | |||
| Pyrexia | 0/40 (0%) | 2/37 (5.4%) | 3/42 (7.1%) | |||
| Xerosis | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Infections and infestations | ||||||
| Bronchitis | 3/40 (7.5%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Conjunctivitis | 4/40 (10%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Cystitis | 0/40 (0%) | 3/37 (8.1%) | 2/42 (4.8%) | |||
| Paronychia | 5/40 (12.5%) | 6/37 (16.2%) | 1/42 (2.4%) | |||
| Rhinitis | 1/40 (2.5%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Urinary tract infection | 2/40 (5%) | 8/37 (21.6%) | 6/42 (14.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 3/40 (7.5%) | 1/37 (2.7%) | 3/42 (7.1%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/40 (2.5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Aspartate aminotransferase increased | 2/40 (5%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Weight decreased | 2/40 (5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 9/40 (22.5%) | 9/37 (24.3%) | 10/42 (23.8%) | |||
| Hypoalbuminaemia | 2/40 (5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Hypokalaemia | 4/40 (10%) | 7/37 (18.9%) | 2/42 (4.8%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/40 (0%) | 3/37 (8.1%) | 3/42 (7.1%) | |||
| Back pain | 1/40 (2.5%) | 6/37 (16.2%) | 6/42 (14.3%) | |||
| Muscle spasms | 4/40 (10%) | 3/37 (8.1%) | 0/42 (0%) | |||
| Muscular weakness | 1/40 (2.5%) | 1/37 (2.7%) | 3/42 (7.1%) | |||
| Musculoskeletal chest pain | 0/40 (0%) | 2/37 (5.4%) | 2/42 (4.8%) | |||
| Myalgia | 1/40 (2.5%) | 4/37 (10.8%) | 6/42 (14.3%) | |||
| Pain in extremity | 1/40 (2.5%) | 4/37 (10.8%) | 2/42 (4.8%) | |||
| Nervous system disorders | ||||||
| Aphasia | 1/40 (2.5%) | 3/37 (8.1%) | 3/42 (7.1%) | |||
| Ataxia | 2/40 (5%) | 3/37 (8.1%) | 4/42 (9.5%) | |||
| Balance disorder | 1/40 (2.5%) | 2/37 (5.4%) | 2/42 (4.8%) | |||
| Brain oedema | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Dizziness | 8/40 (20%) | 9/37 (24.3%) | 12/42 (28.6%) | |||
| Dysarthria | 1/40 (2.5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Headache | 11/40 (27.5%) | 11/37 (29.7%) | 16/42 (38.1%) | |||
| Neuropathy peripheral | 0/40 (0%) | 0/37 (0%) | 4/42 (9.5%) | |||
| Neurotoxicity | 3/40 (7.5%) | 0/37 (0%) | 1/42 (2.4%) | |||
| Paraesthesia | 0/40 (0%) | 0/37 (0%) | 3/42 (7.1%) | |||
| Peripheral sensory neuropathy | 1/40 (2.5%) | 2/37 (5.4%) | 3/42 (7.1%) | |||
| Somnolence | 3/40 (7.5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Tremor | 0/40 (0%) | 1/37 (2.7%) | 3/42 (7.1%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 2/40 (5%) | 2/37 (5.4%) | 2/42 (4.8%) | |||
| Depression | 1/40 (2.5%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| Insomnia | 6/40 (15%) | 5/37 (13.5%) | 4/42 (9.5%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 1/40 (2.5%) | 3/37 (8.1%) | 1/42 (2.4%) | |||
| Urinary incontinence | 0/40 (0%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/40 (7.5%) | 4/37 (10.8%) | 2/42 (4.8%) | |||
| Dyspnoea | 2/40 (5%) | 3/37 (8.1%) | 4/42 (9.5%) | |||
| Epistaxis | 5/40 (12.5%) | 7/37 (18.9%) | 3/42 (7.1%) | |||
| Rhinorrhoea | 2/40 (5%) | 3/37 (8.1%) | 3/42 (7.1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/40 (0%) | 3/37 (8.1%) | 8/42 (19%) | |||
| Dermatitis acneiform | 8/40 (20%) | 2/37 (5.4%) | 0/42 (0%) | |||
| Dry skin | 8/40 (20%) | 5/37 (13.5%) | 1/42 (2.4%) | |||
| Nail disorder | 2/40 (5%) | 2/37 (5.4%) | 2/42 (4.8%) | |||
| Nail dystrophy | 0/40 (0%) | 2/37 (5.4%) | 1/42 (2.4%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 6/40 (15%) | 0/37 (0%) | 7/42 (16.7%) | |||
| Pruritus | 3/40 (7.5%) | 1/37 (2.7%) | 1/42 (2.4%) | |||
| Rash | 15/40 (37.5%) | 20/37 (54.1%) | 4/42 (9.5%) | |||
| Skin lesion | 3/40 (7.5%) | 0/37 (0%) | 0/42 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Other - 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:
NCT01441596
Other Study ID Numbers:
- 1200.67
- 2010-021415-16
First Posted:
Sep 27, 2011
Last Update Posted:
Sep 7, 2015
Last Verified:
Aug 1, 2015