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An open-label, randomized three-arm Phase II trial to explore the efficacy of BIBW 2992 as a single agent versus lapatinib versus trastuzumab in patients with HER2-positive treatment-naïve Stage IIIa locally advanced breast cancer. Additional information will be obtained on the safety profile and pharmacokinetics of BIBW 2992.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIBW 2992 | Experimental | BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE) |
|
| Lapatinib | Active Comparator | Lapatinib tablets 1500 mg daily. |
|
| Trastuzumab | Active Comparator | Trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lapatinib | Drug | lapatinib tablets 1500 mg daily |
| |
| BIBW 2992 |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response (OR) | Objective response (complete or partial) was assessed according to RECIST 1.0 criteria. | Tumour assessments were performed at screening, day 22 and day 43. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Achieved Clinical Benefit (CB) | CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status. | Tumour assessments were performed at screening, day 22 and day 43. |
| Change From Baseline in the Diameter of the Primary Target Lesion. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.44.01001 Boehringer Ingelheim Investigational Site | Houston | Texas | United States | |||
| 1200.44.12008 Boehringer Ingelheim Investigational Site |
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Because of slow enrollment and a high screen-failure rate, recruitment became a challenge and the sponsor chose to terminate the trial prior to reaching the target enrollment of 120 patients.
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| ID | Title | Description |
|---|---|---|
| FG000 | Afatinib 50 mg | Patients received continuous daily dosing with Afatinib 50 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. |
| FG001 | Lapatinib 1500 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE) |
|
| trastuzumab | Drug | trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly |
|
Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion. |
| 3 weeks or 6 weeks |
| Plasma Concentration of Afatinib | Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7 | Day 7 |
| Changes in Biomarker in Tumour Biopsies | Changes in the biomarkers (Phospho-MAP-Kinase (MAPK), Total MAPK expression, EGFR, HER2, Phospho-EGFR and -HER2, Proliferation marker (Ki67 and p27), Apoptotic index (cleaved caspase 3), Phosphate and tensin homolog (PTEN), HER2 homodimerisation by HERmark assay and Phospho AKT) from biopsy tissue. | Screening, day 22, day 43 |
| Brasília |
| Brazil |
| 1200.44.12011 Boehringer Ingelheim Investigational Site | Cachoeiro de Itapemirim | Brazil |
| 1200.44.12012 Boehringer Ingelheim Investigational Site | Campo Grande | Brazil |
| 1200.44.12009 Boehringer Ingelheim Investigational Site | Caxias do Sul | Brazil |
| 1200.44.12010 Boehringer Ingelheim Investigational Site | Goiânia | Brazil |
| 1200.44.12005 Boehringer Ingelheim Investigational Site | Ijuí | Brazil |
| 1200.44.12007 Boehringer Ingelheim Investigational Site | Natal | Brazil |
| 1200.44.12004 Boehringer Ingelheim Investigational Site | Novo Hamburgo | Brazil |
| 1200.44.12001 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1200.44.12013 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1200.44.14002 Boehringer Ingelheim Investigational Site | Bogotá | Colombia |
| 1200.44.14001 Boehringer Ingelheim Investigational Site | Cali | Colombia |
| 1200.44.19005 Boehringer Ingelheim Investigational Site | Cercado | Peru |
| 1200.44.19001 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 1200.44.19004 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 1200.44.19003 Boehringer Ingelheim Investigational Site | San Isidro | Peru |
Patients received continuous daily dosing with Lapatinib 1500 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial.
| FG002 | Trastuzumab | Patients received weekly trastuzumab infusions of 2 mg/kg following a loading dose of 4 mg/kg per SPC. 6 infusions were to be given over 2 treatment courses. |
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Afatinib 50 mg | Patients received continuous daily dosing with Afatinib 50 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. |
| BG001 | Lapatinib 1500 mg | Patients received continuous daily dosing with Lapatinib 1500 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. |
| BG002 | Trastuzumab | Patients received weekly trastuzumab infusions of 2 mg/kg following a loading dose of 4 mg/kg per SPC. 6 infusions were to be given over 2 treatment courses. |
| BG003 | 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 | Objective Response (OR) | Objective response (complete or partial) was assessed according to RECIST 1.0 criteria. | Treated set (TS). TS consisted of all patients who received at least one dose of study medication. | Posted | Number | 95% Confidence Interval | Percentage of participants | Tumour assessments were performed at screening, day 22 and day 43. |
|
|
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Achieved Clinical Benefit (CB) | CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status. | TS | Posted | Number | Participants | Tumour assessments were performed at screening, day 22 and day 43. |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the Diameter of the Primary Target Lesion. | Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion. | TS | Posted | Least Squares Mean | Standard Error | millimeters | 3 weeks or 6 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration of Afatinib | Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 7 |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Changes in Biomarker in Tumour Biopsies | Changes in the biomarkers (Phospho-MAP-Kinase (MAPK), Total MAPK expression, EGFR, HER2, Phospho-EGFR and -HER2, Proliferation marker (Ki67 and p27), Apoptotic index (cleaved caspase 3), Phosphate and tensin homolog (PTEN), HER2 homodimerisation by HERmark assay and Phospho AKT) from biopsy tissue. | TS. The small number of available biomarker samples in this study did not allow for a meaningful statistical analysis. | Posted | Screening, day 22, day 43 |
|
Up to 28 days following the end-of-treatment visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afatinib 50 mg | Patients received continuous daily dosing with Afatinib 50 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. | 0 | 10 | 10 | 10 | ||
| EG001 | Lapatinib 1500 mg | Patients received continuous daily dosing with Lapatinib 1500 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. | 0 | 8 | 8 | 8 | ||
| EG002 | Trastuzumab | Patients received weekly trastuzumab infusions of 2 mg/kg following a loading dose of 4 mg/kg per SPC. 6 infusions were to be given over 2 treatment courses. | 0 | 11 | 8 | 11 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Lymphatic disorder | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Cyanosis | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 14.0 | Systematic Assessment |
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| Visual acuity reduced | Eye disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Lip dry | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Oral discomfort | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Viral sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
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| Urinary retention | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
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| Urinary tract disorder | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Breast mass | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Excessive granulation tissue | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Rash follicular | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
Because of slow enrollment and a high screen-failure rate, recruitment became a challenge and the sponsor chose to terminate the trial prior to reaching the target enrollment of 120 pat. Small number of subjects lead to some shortcomings in analyses.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000077341 | Lapatinib |
| D000077716 | Afatinib |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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| Male |
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| Participants |
|
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
|