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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-011321-14 | EudraCT Number | EudraCT |
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The primary objective of this trial is to determine the Maximum Tolerated Dose (MTD) of the combination of BIBW 2992/BIBF 1120 therapy administered concomitantly. The MTD will provide dosing recommendation for subsequent phase II trials in patients with metastatic cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIBW 2992 + BIBF 1120 | Experimental | This is a phase I dose escalation clinical trial and the data obtained shall determine the MTD for the combination of BIBW 2992/BIBF 1120 in 28-day of treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIBW 2992 | Drug | EGFR inhibitor |
| |
| BIBF 1120 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities | Maximum tolerated dose (MTD) of nintedanib and afatinib based on the Percentage of participants experienced dose limiting toxicities during the dose escalation phase. | first treatment cycle, up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 | The investigator evaluated whether complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) occurred in a patient. CR for target lesions: Disappearance of all target lesions. CR for non-target lesions: Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis). PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study. PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions |
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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 |
|---|---|---|---|---|---|---|
| 1239.14.3301A Boehringer Ingelheim Investigational Site | Villejuif | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26512876 | Derived | Bahleda R, Hollebecque A, Varga A, Gazzah A, Massard C, Deutsch E, Amellal N, Farace F, Ould-Kaci M, Roux F, Marzin K, Soria JC. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours. Br J Cancer. 2015 Nov 17;113(10):1413-20. doi: 10.1038/bjc.2015.374. Epub 2015 Oct 29. |
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Trial consisted of a dose-escalation phase (to determine the maximum tolerated dose (MTD) of treatments administered concomitantly) and an expansion phase(to assess the safety and the preliminary anti-tumour activity of the combination therapy at the previously determined MTD in patients with non-small cell lung cancer or pancreatic adenocarcinoma)
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| ID | Title | Description |
|---|---|---|
| FG000 | Nintedanib 150 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG001 | Nintedanib 150 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG002 | Nintedanib 200 mg +Afatinib 10 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG003 | Nintedanib 200 mg +Afatinib 20 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG004 | Nintedanib 200 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG005 | Nintedanib 200 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| FG006 | Nintedanib 150 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| FG007 | Nintedanib 200 mg +Afatinib 30 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| FG008 | Nintedanib 200 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| FG009 | NSCLC | Patients with non-small cell lung cancer (NSCLC) receiving the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d.) plus film-coated tablet of Afatinib 30 mg (q.d.)). This is a part of the "expansion phase" which follows on the dose-escalation phase. |
| FG010 | Pancreatic Adenocarcinoma | Patients with Pancreatic adenocarcinoma were to be treated with the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg bid plus film-coated tablet of Afatinib 30 mg qd). This is a part of the "expansion phase" which follows on the dose-escalation phase. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set (TS): A treated set (TS) was defined consisting of all patients who received at least one dose of nintedanib or afatinib during the study period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Nintedanib 150 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG001 |
| 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 | Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities | Maximum tolerated dose (MTD) of nintedanib and afatinib based on the Percentage of participants experienced dose limiting toxicities during the dose escalation phase. | TS | Posted | Number | percentage of participants | first treatment cycle, up to 28 days |
|
First treatment administration until cut-off date of 02Oct2014; up to 336 days
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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 | Nintedanib 150 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 30 mg was given continuously once daily (q.d.) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077716 | Afatinib |
| C530716 | nintedanib |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Drug |
VEGF inhibitor |
|
| 6 weeks |
| Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0 | Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0). | First treatment administration until cut-off date of 02Oct2014; up to 336 days |
| Changes in Safety Laboratory Parameters | Changes in safety laboratory Parameters reported as adverse events | First treatment administration until cut-off date of 02 October 2014, up to 336 days |
| Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State) | Cpre,ss,norm (Dose normalized trough plasma concentration of nintedanib at steady state) are presented for the 2 MTD treatment groups (continuous administered nintedanib at 150 mg b.i.d. concomitantly with continuously administered afatinib 30 mg q.d. or with intermittently administered afatinib 40 mg q.d.) As nintedanib is given twice daily, samples are taken at Day 8, Day 15, Day 22 and Day 28; the Pharmacokinetic (PK) parameter names will be Cpre,ss,15,norm (Day 8), Cpre,ss,29,norm (Day 15), Cpre,ss,43,norm (Day 22) and Cpre,ss,55,norm (Day 28) | Day 8, Day 15, Day 22 and Day 28 |
| Trough Plasma Concentration of Afatinib at Steady State | C(pre,ss) is defined as pre-dose (trough) concentration of afatinib in plasma at steady state immediately before administration of the next dose. C24,7 corresponds to the plasma concentration at 24 hours on Day 7. C24,13 corresponds to the plasma concentration at 24 hours on Day 13. C24,27 corresponds to the plasma concentration at 24 hours on Day 27. | Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28 |
| Objective Response (OR) During the Expansion Phase | OR is defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be nonpathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below: CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; All the above scenarios should also satisfy 'No occurrence of new lesions'. | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
| Disease Control (DC) During the Expansion Phase | DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; SD for TL: change in the sum of diameters does not satisfy PR or PD. SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions. | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
| Stable Disease for at Least 12 Weeks During the Expansion Phase | SD: Neither sufficient shrinkage to qualify for PR (Partial response) nor sufficient increase to qualify for PD(Progressive disease), taking as references the smallest sum of diameters SoD while on study. PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters. PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions. | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
| Percentage Change in the Tumour Size From Baseline During the Expansion Phase | Percentage change in the tumour size from baseline is expressed as Number of subjects with maximum decrease from baseline in the sum of longest diameters of target lesions. | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
| Dose limiting or dose reducing toxicity |
|
| Other adverse event |
|
| Refused to continue taking trial med. |
|
| Reason other than those specified above |
|
| Nintedanib 150 mg +Afatinib 40 mg - Continuously |
Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG002 | Nintedanib 200 mg +Afatinib 10 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG003 | Nintedanib 200 mg +Afatinib 20 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG004 | Nintedanib 200 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG005 | Nintedanib 200 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| BG006 | Nintedanib 150 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| BG007 | Nintedanib 200 mg +Afatinib 30 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| BG008 | Nintedanib 200 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| BG009 | NSCLC | Patients with non-small cell lung cancer (NSCLC) receiving the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d.) plus film-coated tablet of Afatinib 30 mg (q.d.)). This is a part of the "expansion phase" which follows on the dose-escalation phase. |
| BG010 | Pancreatic Adenocarcinoma | Patients with Pancreatic adenocarcinoma were to be treated with the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg bid plus film-coated tablet of Afatinib 30 mg qd). This is a part of the "expansion phase" which follows on the dose-escalation phase. |
| BG011 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| OG002 | Nintedanib 200 mg +Afatinib 10 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| OG003 | Nintedanib 200 mg +Afatinib 20 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| OG004 | Nintedanib 200 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| OG005 | Nintedanib 200 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.). This is a part of the "dose-escalation phase". |
| OG006 | Nintedanib 150 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| OG007 | Nintedanib 200 mg +Afatinib 30 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
| OG008 | Nintedanib 200 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week. This is a part of the "dose-escalation phase". |
|
|
| Secondary | Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 | The investigator evaluated whether complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) occurred in a patient. CR for target lesions: Disappearance of all target lesions. CR for non-target lesions: Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis). PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study. PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions | TS | Posted | Number | percentage of participants | 6 weeks |
|
|
|
| Secondary | Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0 | Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0). | TS | Posted | Number | participants | First treatment administration until cut-off date of 02Oct2014; up to 336 days |
|
|
|
| Secondary | Changes in Safety Laboratory Parameters | Changes in safety laboratory Parameters reported as adverse events | TS | Posted | Number | participants | First treatment administration until cut-off date of 02 October 2014, up to 336 days |
|
|
|
| Secondary | Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State) | Cpre,ss,norm (Dose normalized trough plasma concentration of nintedanib at steady state) are presented for the 2 MTD treatment groups (continuous administered nintedanib at 150 mg b.i.d. concomitantly with continuously administered afatinib 30 mg q.d. or with intermittently administered afatinib 40 mg q.d.) As nintedanib is given twice daily, samples are taken at Day 8, Day 15, Day 22 and Day 28; the Pharmacokinetic (PK) parameter names will be Cpre,ss,15,norm (Day 8), Cpre,ss,29,norm (Day 15), Cpre,ss,43,norm (Day 22) and Cpre,ss,55,norm (Day 28) | PKS. Only 6 patients were planned to be treated in the "Nintedanib 150 mg +Afatinib 30 mg- Continuously" group. Nevertheless, the patients were allowed to reduce their dose and by the way they changed the group and came in the "Nintedanib 150 mg +Afatinib 30 mg- Continuously" group with at the end N = 8 evaluable concentrations instead of 6 planned | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/millilitre/milligram (ng/mL/mg) | Day 8, Day 15, Day 22 and Day 28 |
|
|
|
| Secondary | Trough Plasma Concentration of Afatinib at Steady State | C(pre,ss) is defined as pre-dose (trough) concentration of afatinib in plasma at steady state immediately before administration of the next dose. C24,7 corresponds to the plasma concentration at 24 hours on Day 7. C24,13 corresponds to the plasma concentration at 24 hours on Day 13. C24,27 corresponds to the plasma concentration at 24 hours on Day 27. | PKS. Only 6 patients were planned to be treated in the "Nintedanib 150 mg +Afatinib 30 mg- Continuously" group. Nevertheless, the patients were allowed to reduce their dose and by the way they changed the group and came in the "Nintedanib 150 mg +Afatinib 30 mg- Continuously" group with at the end N = 8 evaluable concentrations instead of 6 planned | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/millilitre (ng/mL) | Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28 |
|
|
|
| Secondary | Objective Response (OR) During the Expansion Phase | OR is defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be nonpathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below: CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; All the above scenarios should also satisfy 'No occurrence of new lesions'. | Treated set | Posted | Number | percentage of participants | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
|
|
|
| Secondary | Disease Control (DC) During the Expansion Phase | DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; SD for TL: change in the sum of diameters does not satisfy PR or PD. SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions. | Treated set | Posted | Number | percentage of participants | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
|
|
|
| Secondary | Stable Disease for at Least 12 Weeks During the Expansion Phase | SD: Neither sufficient shrinkage to qualify for PR (Partial response) nor sufficient increase to qualify for PD(Progressive disease), taking as references the smallest sum of diameters SoD while on study. PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters. PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions. | Treated set | Posted | Number | percentage of participants | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
|
|
|
| Secondary | Percentage Change in the Tumour Size From Baseline During the Expansion Phase | Percentage change in the tumour size from baseline is expressed as Number of subjects with maximum decrease from baseline in the sum of longest diameters of target lesions. | Treated set | Posted | Number | participants | Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days) |
|
|
|
| 3 |
| 6 |
| 6 |
| 6 |
| EG001 | Nintedanib 150 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 40 mg was given continuously once daily (q.d.) | 3 | 3 | 3 | 3 |
| EG002 | Nintedanib 200 mg +Afatinib 10 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 10 mg was given continuously once daily (q.d.) | 1 | 3 | 3 | 3 |
| EG003 | Nintedanib 200 mg +Afatinib 20 mg - Continuosly | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 20 mg was given continuously once daily (q.d.) | 0 | 3 | 3 | 3 |
| EG004 | Nintedanib 200 mg +Afatinib 30 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 30 mg was given continuously once daily (q.d.) | 7 | 8 | 8 | 8 |
| EG005 | Nintedanib 200 mg +Afatinib 40 mg - Continuously | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 40 mg was given continuously once daily (q.d.) | 3 | 3 | 3 | 3 |
| EG006 | Nintedanib 150 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week | 1 | 7 | 7 | 7 |
| EG007 | Nintedanib 200 mg +Afatinib 30 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week | 1 | 6 | 6 | 6 |
| EG008 | Nintedanib 200 mg +Afatinib 40 mg - Intermittently | Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, filmcoated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week | 4 | 6 | 6 | 6 |
| EG009 | NSCLC | Patients with non-small cell lung cancer (NSCLC) receiving the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d.) plus film-coated tablet of Afatinib 30 mg (q.d.)). This is a part of the "expansion phase" which follows on the dose-escalation phase. | 7 | 18 | 18 | 18 |
| EG010 | Pancreatic Adenocarcinoma | Patients with Pancreatic adenocarcinoma were to be treated with the study drug combination at the maximum tolerated dose (MTD) level determined for continuous afatinib and nintedanib dosing during the dose-escalation phase (oral administration of soft-gelatine capsule of Nintedanib 150 mg (b.i.d) plus film-coated tablet of Afatinib 30 mg (q.d)). This is a part of the "expansion phase" which follows on the dose-escalation phase. | 3 | 7 | 6 | 7 |
| Thrombotic microangiopathy | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Asthenia | General disorders | 17.1 | Systematic Assessment |
|
| General physical health deterioration | General disorders | 17.1 | Systematic Assessment |
|
| Hyperthermia | General disorders | 17.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | 17.1 | Systematic Assessment |
|
| Pain | General disorders | 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | 17.1 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Hepatotoxicity | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Lung infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Pneumonia pneumococcal | Infections and infestations | 17.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | 17.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | 17.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 17.1 | Systematic Assessment |
|
| Metastases to ovary | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 17.1 | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Subcutaneous nodule | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Oesophageal operation | Surgical and medical procedures | 17.1 | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | 17.1 | Systematic Assessment |
|
| Pyloric stenosis | Congenital, familial and genetic disorders | 17.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | 17.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | 17.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | 17.1 | Systematic Assessment |
|
| Blepharitis | Eye disorders | 17.1 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | 17.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | 17.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | 17.1 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | 17.1 | Systematic Assessment |
|
| Visual impairment | Eye disorders | 17.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Aerophagia | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Glossodynia | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Oesophageal pain | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Oesophagitis haemorrhagic | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Rectal tenesmus | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Tongue coated | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Tongue dry | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 17.1 | Systematic Assessment |
|
| Asthenia | General disorders | 17.1 | Systematic Assessment |
|
| Axillary pain | General disorders | 17.1 | Systematic Assessment |
|
| Chest pain | General disorders | 17.1 | Systematic Assessment |
|
| Chills | General disorders | 17.1 | Systematic Assessment |
|
| Face oedema | General disorders | 17.1 | Systematic Assessment |
|
| Fatigue | General disorders | 17.1 | Systematic Assessment |
|
| Feeling hot | General disorders | 17.1 | Systematic Assessment |
|
| Inflammation | General disorders | 17.1 | Systematic Assessment |
|
| Mucosal dryness | General disorders | 17.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | 17.1 | Systematic Assessment |
|
| Oedema | General disorders | 17.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | 17.1 | Systematic Assessment |
|
| Pain | General disorders | 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | 17.1 | Systematic Assessment |
|
| Thirst | General disorders | 17.1 | Systematic Assessment |
|
| Xerosis | General disorders | 17.1 | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | 17.1 | Systematic Assessment |
|
| Iodine allergy | Immune system disorders | 17.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Ear infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Folliculitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Furuncle | Infections and infestations | 17.1 | Systematic Assessment |
|
| Genital infection fungal | Infections and infestations | 17.1 | Systematic Assessment |
|
| Herpes virus infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Lung infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Lymphangitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Oral fungal infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | 17.1 | Systematic Assessment |
|
| Paronychia | Infections and infestations | 17.1 | Systematic Assessment |
|
| Purulent discharge | Infections and infestations | 17.1 | Systematic Assessment |
|
| Rash pustular | Infections and infestations | 17.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Skin infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Tracheitis | Infections and infestations | 17.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 17.1 | Systematic Assessment |
|
| Gastroenteritis radiation | Injury, poisoning and procedural complications | 17.1 | Systematic Assessment |
|
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | 17.1 | Systematic Assessment |
|
| Medication error | Injury, poisoning and procedural complications | 17.1 | Systematic Assessment |
|
| Periorbital haemorrhage | Injury, poisoning and procedural complications | 17.1 | Systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | 17.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | 17.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | 17.1 | Systematic Assessment |
|
| Blood fibrinogen increased | Investigations | 17.1 | Systematic Assessment |
|
| Ejection fraction decreased | Investigations | 17.1 | Systematic Assessment |
|
| Electrocardiogram repolarisation abnormality | Investigations | 17.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | 17.1 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | 17.1 | Systematic Assessment |
|
| Troponin increased | Investigations | 17.1 | Systematic Assessment |
|
| Weight decreased | Investigations | 17.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Metabolic acidosis | Metabolism and nutrition disorders | 17.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Clubbing | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Trismus | Musculoskeletal and connective tissue disorders | 17.1 | Systematic Assessment |
|
| Cervical root pain | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Motor dysfunction | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Parosmia | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | 17.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Expressive language disorder | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Libido disorder | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Psychomotor retardation | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | 17.1 | Systematic Assessment |
|
| Calculus urinary | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Incontinence | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Urinary bladder haemorrhage | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | 17.1 | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | 17.1 | Systematic Assessment |
|
| Gynaecomastia | Reproductive system and breast disorders | 17.1 | Systematic Assessment |
|
| Vulvovaginal discomfort | Reproductive system and breast disorders | 17.1 | Systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | 17.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Rhinalgia | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 17.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Hypertrichosis | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Macule | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Nail dystrophy | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Nail growth abnormal | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Nail ridging | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Scab | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin burning sensation | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin toxicity | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Solar dermatitis | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Xeroderma | Skin and subcutaneous tissue disorders | 17.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | 17.1 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | 17.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | 17.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | 17.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | 17.1 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | 17.1 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 17.1 | Systematic Assessment |
|
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 17.1 | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 17.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Partial response |
|
| Stable disease |
|
| Progressive disease |
|
| CTCAE Grade 2 |
|
| CTCAE Grade 3 |
|
| CTCAE Grade 4 |
|
| CTCAE Grade 5 |
|
| Aspartate aminotransferase increased |
|
| Blood creatinine increased |
|
| Blood alkaline phosphatase increased |
|
| Blood bilirubin increased |
|
| Troponin increased |
|
| Gamma-glutamyltransferase increased |
|
| Blood creatinine phosphokinase increased |
|
| Blood fibrinogen increased |
|
| Hepatic enzymes increased |
|
| Cpre,ss,43,norm (N= 5, 6) |
|
| Cpre,ss,55,norm (N= 8, NA) |
|
| Cpre,ss,28 (N= 8, NA) |
|
| C24,7 (N= NA, 6) |
|
| C24,13 (N= NA, 5) |
|
| C24,27 (N= NA, 2) |
|
| Missing |
|
| Missing |
|
| Missing |
|
| >-30% and <0% |
|
| <-30% |
|