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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-015911-42 | EudraCT Number | EudraCT |
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The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib.
Overall safety, pharmacokinetics and anti-tumor activity for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib, gefitinib or BIBW 2992 will be evaluated as secondary objectives.
Initially a standard, 3+3 dose escalation will be performed to determine the MTD of BIBW 2992 when administered together with cetuximab in patients with advanced non small cell lung cancer and acquired resistance to erlotinib or gefitinib.
Subsequently, the preliminary efficacy and safety of the identified MTD of cetuximab administered with BIBW 2992 will be explored in a combo arm via a further expansion of MTD cohort up to a total of 140 EGFR mutation positive NSCLC with acquired resistance to erlotinib/gefitinib.
Furthermore, the safety and preliminary anti-tumor activity of the combination therapy in EGFR mutant NSCLC patients who developed acquired resistance (AR) to BIBW 2992, will be assessed in a sequential arm. The sequential arm will use a two-stage design with an early stopping rule after 12 patients with acquired resistance to BIBW 2992 have received up to 5 courses of BIBW 2992 plus cetuximab. If no responses are seen in 12 patients during 5 courses of combination therapy, accrual in the sequential arm will stop. If 1 or more responses are observed, the sequential arm will expand up to about 40 patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| combination arm | Experimental | patients to receive medium BIBW 2992 once daily plus biweekly cetuximab infusion at low, median and high dose level |
|
| sequential arm | Experimental | patients to receive BIBW 2992 once daily, upon progression add biweekly cetuximab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab | Drug | BIBW 2992 medium dose plus high dose level of cetuximab |
| |
| Measure | Description | Time Frame |
|---|---|---|
| The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT). | A DLT was defined as an AE or laboratory abnormality that a) related to the study regimen; b) or met any of the following criteria:
| from day 1 treatment until progression or undue toxicity, up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Highest CTCAE Grade | Safety of afatinib when administered together with cetuximab as indicated by intensity and incidence of adverse events, graded according to the U.S. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version (v) 3.0 | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
Not provided
Inclusion criteria:
1) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. A tumor which harbors exon 20 insertion or de novo T790M mutation is eligible for the treatment in the sequential arm 2) Objective clinical benefit from treatment with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) as defined by either
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.71.1004 Boehringer Ingelheim Investigational Site | Aurora | Colorado | United States | |||
| 1200.71.1003 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29110849 | Derived | Horn L, Gettinger S, Camidge DR, Smit EF, Janjigian YY, Miller VA, Pao W, Freiwald M, Fan J, Wang B, Chand VK, Groen HJM. Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer. 2017 Nov;113:51-58. doi: 10.1016/j.lungcan.2017.08.014. Epub 2017 Aug 31. | |
| 25074459 |
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171 patients were entered and treated in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Total Patients | All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set which includeed all patients enrolled in the trial who were documented to have taken at least one dose of study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Total Patients | All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT). | A DLT was defined as an AE or laboratory abnormality that a) related to the study regimen; b) or met any of the following criteria:
| Treated set for Cohort One. Cohort one was based on the data from the first treatment cycle where four patients received 'Afatinib 40+Cetuximab 250' and six patients received 'Afatinib 40+Cetuximab 500'. | Posted | Number | participants | from day 1 treatment until progression or undue toxicity, up to 28 days |
Up to 915 days
32 patients in the 'Afa40-mono' group had disease progression and were transitioned to treatment with 'Afa40+Ctx500'. Thus the total of 203 patients (4+126+37+36) minus the 321 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
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 | Combination Arm - Afa40+Ctx250 | Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| D000077716 | Afatinib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
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| Cetuximab |
| Drug |
BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added |
|
| BIBW 2992 | Drug | BIBW 2992 medium dose plus high dose level of cetuximab |
|
| BIBW 2992 | Drug | BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added |
|
| Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
| Frequency (%) of Patients With Adverse Events Leading to Dose Reduction | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
| Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation | Frequency (%) of patients with adverse events leading to treatment discontinuation | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
| Frequency (%) of Patients With Adverse Events Leading to Death | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
| Frequency (%) of Patients With Related Serious Adverse Events | Frequency (%) of patients with drug-related serious adverse events | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
| Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm | Area Under the Concentration-time Curve (AUC) of Afatinib in plasma at steady state over a uniform dosing interval tau (15 days) (AUCtau,ss) after oral administration of Afatinib and cetuximab combination therapy | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| Concentration of Afatinib in Plasma for the Combination Arm | Minimum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmin,ss). Maximum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmax,ss). | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| Peak-trough Fluctuation (PTF) | Peak-trough fluctuation (PTF) of plasma afatinib for the combination arm. PTF = 100*(Cmax-Cmin)/Caverage where Caverage = AUC/time, where time equals 24 hours. | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| t1/2,ss | Terminal half-life of Afatinib in plasma at steady state (t1/2,ss) | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| MRTpo,ss | mean residence time of Afatinib in the body at steady state after oral administration (MRTpo,ss) for 15 days | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| CL/F,ss,15 | Apparent clearance of afatinib in plasma at steady state after extravascular multiple dose administration (CL/F,ss) | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| Vz/F,ss | Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss) for 15 days | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
| Predose Plasma Concentrations of Afatinib for the Combination Arm | Predose plasma concentrations (Cpre,ss) of Afatinib at Course 1, Visit 2, 3, 4 and 5, at Course 2, Visit 1 and 2 and at Course 3, Visit 1. | Up to 57 days |
| Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Disease control = CR + PR + SD. | up to 116 weeks |
| Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Objective tumor response = CR + PR. | up to 116 weeks |
| Duration of Objective Response (According to RECIST v1.1) | Duration of objective response was measured from the time measurements criteria were met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since treatment started). | up to 116 weeks |
| Duration of Disease Control (According to RECIST v1.1) | Duration of disease control was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence SD, PR or CR. | up to 116 weeks |
| Progression-Free Survival (PFS) Time | Progression-Free Survival was defined as the duration of time from start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to RECIST 1.1) or death. | up to 116 weeks |
| New Haven |
| Connecticut |
| United States |
| 1200.71.1001 Boehringer Ingelheim Investigational Site | New York | New York | United States |
| 1200.71.1002 Boehringer Ingelheim Investigational Site | Nashville | Tennessee | United States |
| 1200.71.2002 Boehringer Ingelheim Investigational Site | Amsterdam | Netherlands |
| 1200.71.2001 Boehringer Ingelheim Investigational Site | Groningen | Netherlands |
| Derived |
| Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326. Epub 2014 Jul 29. |
| Refusal to start/continue medication |
|
| Other reason not defined above |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Combination Arm - Afa40+Ctx250 | Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with Acquired Resistance (AR) to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250) |
| OG001 | Combination Arm - Afa40+Ctx500 | Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500) |
|
|
| Secondary | Highest CTCAE Grade | Safety of afatinib when administered together with cetuximab as indicated by intensity and incidence of adverse events, graded according to the U.S. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version (v) 3.0 | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Frequency (%) of Patients With Adverse Events Leading to Dose Reduction | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation | Frequency (%) of patients with adverse events leading to treatment discontinuation | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Frequency (%) of Patients With Adverse Events Leading to Death | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Frequency (%) of Patients With Related Serious Adverse Events | Frequency (%) of patients with drug-related serious adverse events | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | From first drug administration to 28 days after discontinuation of drug intake up to 915 days |
|
|
|
| Secondary | Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm | Area Under the Concentration-time Curve (AUC) of Afatinib in plasma at steady state over a uniform dosing interval tau (15 days) (AUCtau,ss) after oral administration of Afatinib and cetuximab combination therapy | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | Concentration of Afatinib in Plasma for the Combination Arm | Minimum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmin,ss). Maximum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmax,ss). | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | Peak-trough Fluctuation (PTF) | Peak-trough fluctuation (PTF) of plasma afatinib for the combination arm. PTF = 100*(Cmax-Cmin)/Caverage where Caverage = AUC/time, where time equals 24 hours. | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | % of average concentration | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | t1/2,ss | Terminal half-life of Afatinib in plasma at steady state (t1/2,ss) | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | MRTpo,ss | mean residence time of Afatinib in the body at steady state after oral administration (MRTpo,ss) for 15 days | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | CL/F,ss,15 | Apparent clearance of afatinib in plasma at steady state after extravascular multiple dose administration (CL/F,ss) | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | Vz/F,ss | Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss) for 15 days | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 |
|
|
|
| Secondary | Predose Plasma Concentrations of Afatinib for the Combination Arm | Predose plasma concentrations (Cpre,ss) of Afatinib at Course 1, Visit 2, 3, 4 and 5, at Course 2, Visit 1 and 2 and at Course 3, Visit 1. | Pharmacokinetic dataset (PKS) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Up to 57 days |
|
|
|
| Secondary | Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Disease control = CR + PR + SD. | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | 95% Confidence Interval | percentage of patients | up to 116 weeks |
|
|
|
| Secondary | Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Objective tumor response = CR + PR. | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Number | percentage of patients | up to 116 weeks |
|
|
|
| Secondary | Duration of Objective Response (According to RECIST v1.1) | Duration of objective response was measured from the time measurements criteria were met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since treatment started). | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Mean | Standard Deviation | months | up to 116 weeks |
|
|
|
| Secondary | Duration of Disease Control (According to RECIST v1.1) | Duration of disease control was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence SD, PR or CR. | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Mean | Standard Deviation | months | up to 116 weeks |
|
|
|
| Secondary | Progression-Free Survival (PFS) Time | Progression-Free Survival was defined as the duration of time from start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to RECIST 1.1) or death. | Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section. | Posted | Median | 95% Confidence Interval | months | up to 116 weeks |
|
|
|
| 3 |
| 4 |
| 4 |
| 4 |
| EG001 | Combination Arm - Afa40+Ctx500 | Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500) | 63 | 126 | 126 | 126 |
| EG002 | Sequential Arm - Afatanib Monotherapy (Afa40 Mono) | Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib) Afatinib 40 mg (Afa40 Mono) | 12 | 37 | 36 | 37 |
| EG003 | Sequential Arm - Combination Therapy (Afa40+Ctx500) | Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500) | 15 | 36 | 36 | 36 |
| Atrial fibrillation | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Steroid withdrawal syndrome | Endocrine disorders | MedDRA 17.1 | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Infectious pleural effusion | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Meningitis aseptic | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Streptococcal infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Biopsy lung | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Drug withdrawal headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Embolic cerebral infarction | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain management | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
|
| Surgery | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ear pruritus | Ear and labyrinth disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 17.1 | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA 17.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Glossodynia | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Large intestinal haemorrhage | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Tongue ulceration | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Xerosis | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Eyelid infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Nail infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Appetite disorder | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haemoglobinuria | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hirsutism | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Skin hypertrophy | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Intra-abdominal haematoma | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
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.
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Patients with highest CTCAE Grade 2 |
|
| Patients with highest CTCAE Grade 3 |
|
| Patients with highest CTCAE Grade 4 |
|
| Patients with highest CTCAE Grade 5 |
|
| White blood cell ct. - low (N=4,124,35,35) |
|
| Neutrophils - low (N=4,124,35,35) |
|
| Sodium - low (N=4,124,35,35) |
|
| Potassium - low (N=4,124,35,35) |
|
| Potassium - high (N=4,124,35,35) |
|
| Calcium - low (N=4,124,35,35) |
|
| Calcium - high (N=4,124,35,35) |
|
| Magnesium - low (N=4,124,34,35) |
|
| AST/GOT, SGOT - high (N=4,123,35,35) |
|
| ALT/GPT, SGPT - high (N=4,123,35,35) |
|
| Alkaline phosphatase - high (N=4,124,35,35) |
|
| Blood urea nitrogen - high (N=missing,105,28,28) |
|
| Creatinine - high (N=4,123,33,35) |
|
| Creatinine clearance - low (N=4,123,33,35) |
|
| Bilirubin,total - high (N=4,124,35,35) |
|
| Sodium - high (N=4,124,35,35) |
|
| Cpre,ss,16 (N=3,0) |
|
| Cpre,ss,22 (N=3,21) |
|
| Cpre,ss,29 (N=3,20) |
|
| Cpre,ss,43 (N=3,19) |
|
| Cpre,ss,57 (N=3,0) |
|