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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-003926-40 | EudraCT Number | EudraCT |
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The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events when combined with a platinum therapy (cisplatin or carboplatin).
Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727 combination treatment with cisplatin and carboplatin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A. BI 6727-cisplatin | Experimental | patient to receive 3-weekly infusion escalating dose of BI 6727 combined to cisplatin |
|
| B. BI 6727-carboplatin | Experimental | patient to receive 3-weekly infusion escalating dose of BI 6727 combined to carboplatin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI-6727 | Drug | Low to high dose (administered every 3 weeks). Depending on the toxicities observed, intermediary dose levels may be added |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose | The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin. 0=not maximum tolerated dose, 1=was maximum tolerated dose. | 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities | Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle. | 3 weeks |
| Objective Response Rate | Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0). Tumour response was documented using appropriate techniques |
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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 |
|---|---|---|---|---|---|---|
| 1230.6.3201 Boehringer Ingelheim Investigational Site | Brussels | Belgium | ||||
| 1230.6.3202 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25794535 | Derived | Awada A, Dumez H, Aftimos PG, Costermans J, Bartholomeus S, Forceville K, Berghmans T, Meeus MA, Cescutti J, Munzert G, Pilz K, Liu D, Schoffski P. Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity. Invest New Drugs. 2015 Jun;33(3):611-20. doi: 10.1007/s10637-015-0223-9. Epub 2015 Mar 22. |
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For the carboplatin arm, the target doses were calculated using the Calvert formula to achieve AUC 4, AUC 5 and AUC 6. Calvert formula: Dose (mg) = target AUC x (glomerular filtration rate (GFR) + 25); GFR = (140 - age [years]) x (actual weight [kg])/(72 x serum creatinine [mg/dL]). Multiply by another factor of 0.85 if female).
An open-label, parallel group, 3+3 dose escalation trial Volasertib and cisplatin or carboplatin combination therapy was given on Day 1 of up to 6, 3-week cycles.
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| ID | Title | Description |
|---|---|---|
| FG000 | V200+Cis75 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG001 | V300+Cis75 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG002 | V300+Cis100 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 100mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG003 | V350+Cis75 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG004 | V100+Car4 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC4 (area under the curve of 4) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG005 | V100+Car5 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG006 | V200+Car5 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG007 | V300+Car5 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG008 | V300+Car6 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC6 (area under the curve of 6) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG009 | V350+Car5 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG010 | V100+Cis60 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 60mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| FG011 | V100+Cis75 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Discont. Before Start of Treat. Cycle 2 |
|
| ||||||||||||||||||
| Treated in and Beyond Treat. Cycle 2 |
|
Treated set which included all patients who received at least one administration of volasertib and cisplatin or carboplatin.
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| ID | Title | Description |
|---|---|---|
| BG000 | V200+Cis75 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG001 | V300+Cis75 |
| 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 | The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin. 0=not maximum tolerated dose, 1=was maximum tolerated dose. | Treated set | Posted | Number | Units on a scale | 3 weeks |
|
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 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 | V200+Cis75 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C541363 | BI 6727 |
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| BI 6727 | Drug | low to high dose |
|
| From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Duration of Objective Response | Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria. Tumour response was documented using appropriate techniques | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Best Overall Response | Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria. | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Disease Control Rate | Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria. | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Duration of Disease Control | Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first. | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Progression-free Survival | Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first. | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Incidence and Intensity of Adverse Events According to CTCAE Version 3.0 | Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0 | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Percentage of Participants With Serious Adverse Events | Percentage of participants with serious adverse events (AEs) | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Percentage of Participants With Significant Adverse Events | Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE. DLTs (i.e. significant AEs) per protocol were:
| From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Total Plasma Clearance After Intravascular Administration (CL) | Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1. | 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion |
| Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1. | 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion |
| Change From Baseline in Pulse Rate | Change from baseline in pulse rate at last value on treatment | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Change From Baseline in Neutrophils | Change from baseline in neutrophils with the maximum value on treatment | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Change From Baseline in Platelets | Change from baseline in platelets with the maximum value on treatment | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils | Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils >=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets | Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets >=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment. Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment. Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE) | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment. Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment. Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE) | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Worst CTCAE Grade on Treatment for Platelets | Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Worst CTCAE Grade on Treatment for Neutrophils | Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
| Leuven |
| Belgium |
| Dose Limiting Toxicity (DLT) |
|
| Other adverse events |
|
| Withdrawal by Subject |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG002 | V300+Cis100 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 100mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG003 | V350+Cis75 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG004 | V100+Car4 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC4 (area under the curve of 4) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG005 | V100+Car5 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG006 | V200+Car5 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG007 | V300+Car5 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG008 | V300+Car6 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC6 (area under the curve of 6) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG009 | V350+Car5 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG010 | V100+Cis60 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 60mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG011 | V100+Cis75 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| BG012 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle.
| OG002 | V200+Cis75 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG003 | V300+Cis75 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG004 | V300+Cis100 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 100mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG005 | V350+Cis75 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG006 | V100+Car4 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC4 (area under the curve of 4) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG007 | V100+Car5 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG008 | V200+Car5 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG009 | V300+Car5 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG010 | V300+Car6 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC6 (area under the curve of 6) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
| OG011 | V350+Car5 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. |
|
|
| Secondary | Percentage of Participants With Dose Limiting Toxicities | Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle. | Treated set. There was one patient in the V300+Car6 group whose DLT data was not evaluable, so only 12 patients had evaluable data. | Posted | Number | Percentage of participants | 3 weeks |
|
|
|
| Secondary | Objective Response Rate | Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0). Tumour response was documented using appropriate techniques | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Duration of Objective Response | Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria. Tumour response was documented using appropriate techniques | Treated set restricted to participants with confirmed objective response. | Posted | Median | Full Range | Days | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Best Overall Response | Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria. | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Disease Control Rate | Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria. | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Duration of Disease Control | Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first. | Treated set restricted to participants with confirmed disease control. | Posted | Median | Standard Deviation | Days | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Progression-free Survival | Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first. | Treated set | Posted | Median | Full Range | Days | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Incidence and Intensity of Adverse Events According to CTCAE Version 3.0 | Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0 | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Percentage of Participants With Serious Adverse Events | Percentage of participants with serious adverse events (AEs) | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Percentage of Participants With Significant Adverse Events | Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE. DLTs (i.e. significant AEs) per protocol were:
| Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Total Plasma Clearance After Intravascular Administration (CL) | Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1. | Pharmacokinetic (PK) set which included all participants in the treated set with evaluable PK data | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion |
|
|
|
| Secondary | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Litres | 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion |
|
|
|
| Secondary | Change From Baseline in Pulse Rate | Change from baseline in pulse rate at last value on treatment | Treated set | Posted | Mean | Standard Deviation | bpm | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Change From Baseline in Neutrophils | Change from baseline in neutrophils with the maximum value on treatment | Treated set | Posted | Mean | Standard Deviation | 10^9 cells /L | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Change From Baseline in Platelets | Change from baseline in platelets with the maximum value on treatment | Treated set | Posted | Mean | Standard Deviation | 10^9 cells /L | Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils | Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils >=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets | Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets >=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment. Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment. Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE) | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment. Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment | Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment. Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE) | Treated set | Posted | Number | Percentage of participants | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Worst CTCAE Grade on Treatment for Platelets | Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Units on a scale | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| Secondary | Worst CTCAE Grade on Treatment for Neutrophils | Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE). | Treated set | Posted | Number | Units on a scale | From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days |
|
|
|
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | V300+Cis75 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 1 | 3 | 3 | 3 |
| EG002 | V300+Cis100 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 100mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 6 | 12 | 12 | 12 |
| EG003 | V350+Cis75 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 3 | 6 | 6 | 6 |
| EG004 | V100+Car4 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC4 (area under the curve of 4) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 1 | 3 | 3 | 3 |
| EG005 | V100+Car5 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 0 | 3 | 3 | 3 |
| EG006 | V200+Car5 | Patients received 200mg Volasertib (V200) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 1 | 3 | 3 | 3 |
| EG007 | V300+Car5 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 1 | 6 | 6 | 6 |
| EG008 | V300+Car6 | Patients received 300mg Volasertib (V300) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC6 (area under the curve of 6) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 6 | 13 | 13 | 13 |
| EG009 | V350+Car5 | Patients received 350mg Volasertib (V350) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus AUC5 (area under the curve of 5) carboplatin (Car) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 2 | 3 | 3 | 3 |
| EG010 | V100+Cis60 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 60mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 2 | 3 | 3 | 3 |
| EG011 | V100+Cis75 | Patients received 100mg Volasertib (V100) administered by intravenous infusion over 2 hours at day 1 of each treatment cycle, plus 75mg/m2 cisplatin (Cis) administered by intravenous infusion over 1 hour at day 1 of each treatment cycle. | 1 | 3 | 3 | 3 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Systemic inflammatory response syndrome | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.1 | Systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.1 | Systematic Assessment |
|
| Tumour compression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.1 | Systematic Assessment |
|
| Paraparesis | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Axillary vein thrombosis | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Jugular vein thrombosis | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 14.1 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA 14.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 14.1 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 14.1 | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA 14.1 | Systematic Assessment |
|
| Ophthalmoplegia | Eye disorders | MedDRA 14.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 14.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Duodenitis | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Faecal vomiting | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Regurgitation | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Catheter site phlebitis | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Hepatitis B | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Neutrophil count | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Troponin T increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Cauda equina syndrome | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Bradyphrenia | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pyuria | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Capillaritis | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
| Phlebitis superficial | Vascular disorders | MedDRA 14.1 | 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.
| Partial response |
|
| Stable disease |
|
| Progressive disease |
|
| Non evaluable |
|
| No post-baseline tumour assessment |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| Baseline=0, last value=1 |
|
| Baseline=1, last value=0 |
|
| Baseline=0, last value=2 |
|
| Baseline=0, last value=3 |
|
| Baseline=1, last value=1 |
|
| Baseline=0, last value=1 |
|
| Baseline=0, last value=3 |
|
| Baseline=1, last value=1 |
|
| Baseline=0, last value=2 |
|
| Baseline=0, last value=4 |
|
| Baseline=1, last value=0 |
|
| Baseline=0, worst value=1 |
|
| Baseline=0, worst value=2 |
|
| Baseline=0, worst value=3 |
|
| Baseline=1, worst value=1 |
|
| Baseline=0, worst value=4 |
|
| Baseline=1, worst value=4 |
|
| Baseline=1, worst value=0 |
|
| Baseline=0, worst value=1 |
|
| Baseline=0, worst value=2 |
|
| Baseline=0, worst value=3 |
|
| Baseline=0, worst value=4 |
|
| Baseline=1, worst value=3 |
|
| Baseline=1, worst value=4 |
|