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The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 in Asian cancer patients, and to provide safety data in terms of drug-related adverse events.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 6727 | Experimental | Schedule A |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 6727 | Drug | Dose level 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | Primary objective for this trial was to identify the MTD of volasertib for 2 dosing schedules. The MTD was defined as the highest volasertib dose studied for which the incidence of DLT was less than 2/6 patients. The MTD was defined on the basis of DLTs observed during the first treatment course only. In this outcome measure the percentage of participants with DLTs in cycle 1 is presented. | From first administration of study drug up to 3 weeks |
| MTD of Volasertib | Primary objective for this trial was to identify the MTD of volasertib for 2 dosing schedules. The MTD was defined as the highest volasertib dose studied for which the incidence of DLT was less than 2/6 patients. This outcome measure shows the MTD. | From the first administration of study drug up to 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 | Percentage of participants with incidence and intensity of drug-related AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. This endpoint will be presented as a percentage of patients with adverse event by treatment and the highest CTCAE grade of the related AE. | From first administration of volasertib to 21 days after the last dose, up to 548 days |
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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 |
|---|---|---|---|---|---|---|
| 1230.16.886002 Boehringer Ingelheim Investigational Site | Tainan | Taiwan | ||||
| 1230.16.886001 Boehringer Ingelheim Investigational Site |
Investigator notified the sponsor if a patient qualified for study participation. Sponsor informed the investigator about the respective treatment schedule and the dose tier. After completing dose level 1 of D1 schedule (i.e. 100mg), dose level 2 of D1 schedule (i.e. 200mg) and dose level 1 of D1+D8 schedule (50mg on Days 1+8,every 3 weeks) started
A Phase I single dose escalation study of two dosing schedules of Volasertib administered intravenously in Asian patients with various solid cancers with repeated administration in patients with clinical benefit
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| ID | Title | Description |
|---|---|---|
| FG000 | V 100 mg D1 | A single dose of 100 milligram (mg) volasertib (V) on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 minutes (min) using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 millilitre (mL) physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly intravenous (i.v.). |
| FG001 | V 200 mg D1 | A single dose of 200 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG002 | V 250 mg D1 | A single dose of 250 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG003 | V 300 mg D1 | A single dose of 300 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG004 | V 350 mg D1 | A single dose of 350 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG005 | V 50 mg D1, D8 | A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG006 | V 100 mg D1, D8 | A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG007 | V 150 mg D1, D8 | A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| FG008 | V 200 mg D1, D8 | A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The treated set consisted of all patients who received at least one dose of volasertib.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | V100 D1 | A single dose of 100 mg volasertib on Day 1 every 3-week course. |
| BG001 | V200 D1 | A single dose of 200 mg volasertib on Day 1 every 3-week course. |
| 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 | Percentage of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | Primary objective for this trial was to identify the MTD of volasertib for 2 dosing schedules. The MTD was defined as the highest volasertib dose studied for which the incidence of DLT was less than 2/6 patients. The MTD was defined on the basis of DLTs observed during the first treatment course only. In this outcome measure the percentage of participants with DLTs in cycle 1 is presented. | The treated set consisted of all patients whe received at least one dose of volasertib. | Posted | Number | percentage of participants | From first administration of study drug up to 3 weeks |
|
From inclusion into the study to 21 days after last drug administration (up to 548 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 | V100 D1 | A single dose of 100 mg volasertib on Day 1 every 3-week course. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C541363 | BI 6727 |
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| Change From Baseline to Last Value on Treatment in Platelets | This endpoint will be presented as a change from baseline to last value on treatment in platelets. | Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days) |
| Change From Baseline to Last Value on Treatment in Neutrophils | This endpoint will be presented as a change from baseline to last value on treatment in neutrophils. | Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days) |
| Patient Performance | This endpoint will present the best clinical assessment. The investigator will perform a clinical assessment. An evaluation will be done whether the patient appears to be clinically improved, unchanged, or deteriorated. The presented numbers show the percentage of patients. | From first administration of volasertib to the last dose, up to 527 days |
| Vital Signs (Blood Pressure) | This endpoint will be presented as a change from baseline at last observation of systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeter of mercury (mmHg) and pulse rate (PR) in beats per minute (bpm). In this outcome measure SBP and DBP are presented. | Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days) |
| Vital Signs (Pulse Rate) | This endpoint will be presented as a change from baseline at last observation of systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeter of mercury (mmHg) and pulse rate (PR) in beats per minute (bpm). In this outcome measure the pulse rate is presented. | Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days) |
| ECG | This endpoint will be presented as a change from individual baseline in QT interval, corrected according to Fridericias formula (QTcF) to end of infusion (2 hours) and 24 hours after first infusion in Cycle 1. | Baseline, 2 hours (before the end of infusion of volasertib) and 24 hours after first infusion in Cycle 1 |
| Objective Response | The objective response (OR) was defined as complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest) assessed by tumour measurement and evaluated according to the Response Evaluation Criteria in solid tumours (RECIST), version 1.0. The data represents the percentage of patients. | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
| Progression-free Survival | Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. PFS was assessed by tumour measurement and evaluated according to RECIST, version 1.0. | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
| Response Duration | The duration of overall response was measured from the time measurement criteria were met for complete response (CR) or partial response (PR), whichever was recorded first, until the first date that recurrent or progressive disease was objectively documented. The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. | From first drug administration up to at 3 month interval after final End of treatment visit until disease progression, death, or lost to follow-up, up to 548 days |
| Disease Control | The disease control (DC) presented are the percentage of patients with CR, PR or stable disease as best response throughout the study assessed by tumour measurement and evaluated according to RECIST, version 1.0. | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
| Sum of the Largest Diameters of Target Lesions | The individual time profile of the sum of the largest diameters of target lesions (LD) is presented graphically for each patient in the Clinical Trial Report (CTR) only. No descriptive statistics were planned. | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
| Pharmacokinetics (PK) AUC0-∞ of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure AUC0-∞ is presented. | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
| Pharmacokinetics (PK) AUC0-168 of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure AUC0-168 is presented. | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
| Pharmacokinetics (PK) Cmax of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure Cmax is presented. | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
| Taipei |
| Taiwan |
| Dose limiting Toxicity (DLT) |
|
| Other Adverse Event |
|
| Refused cont. medication |
|
| Not specified above |
|
| BG002 | V250 D1 | A single dose of 250 mg volasertib on Day 1 every 3-week course. |
| BG003 | V300 D1 | A single dose of 300 mg volasertib on Day 1 every 3-week course. |
| BG004 | V350 D1 | A single dose of 350 mg volasertib on Day 1 every 3-week course. |
| BG005 | V50 D1, D8 | A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. |
| BG006 | V100 D1, D8 | A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. |
| BG007 | V150 D1, D8 | A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. |
| BG008 | V200 D1, D8 | A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. |
| BG009 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| V200 D1 |
A single dose of 200 mg volasertib on Day 1 every 3-week course. |
| OG002 | V250 D1 | A single dose of 250 mg volasertib on Day 1 every 3-week course. |
| OG003 | V300 D1 | A single dose of 300 mg volasertib on Day 1 every 3-week course. |
| OG004 | V350 D1 | A single dose of 350 mg volasertib on Day 1 every 3-week course. |
| OG005 | V50 D1, D8 | A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. |
| OG006 | V100 D1, D8 | A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. |
| OG007 | V150 D1, D8 | A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. |
| OG008 | V200 D1, D8 | A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. |
|
|
| Primary | MTD of Volasertib | Primary objective for this trial was to identify the MTD of volasertib for 2 dosing schedules. The MTD was defined as the highest volasertib dose studied for which the incidence of DLT was less than 2/6 patients. This outcome measure shows the MTD. | The treated set. | Posted | Number | milligram (mg) | From the first administration of study drug up to 3 weeks |
|
|
|
| Secondary | Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 | Percentage of participants with incidence and intensity of drug-related AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. This endpoint will be presented as a percentage of patients with adverse event by treatment and the highest CTCAE grade of the related AE. | Treated Set | Posted | Number | Percentage of participants | From first administration of volasertib to 21 days after the last dose, up to 548 days |
|
|
|
| Secondary | Change From Baseline to Last Value on Treatment in Platelets | This endpoint will be presented as a change from baseline to last value on treatment in platelets. | Treated Set | Posted | Mean | Standard Deviation | 10^9 platelets/ Litre (L) | Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days) |
|
|
|
| Secondary | Change From Baseline to Last Value on Treatment in Neutrophils | This endpoint will be presented as a change from baseline to last value on treatment in neutrophils. | Treated Set | Posted | Mean | Standard Deviation | 10^9 neutrophils / Litre (L) | Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days) |
|
|
|
| Secondary | Patient Performance | This endpoint will present the best clinical assessment. The investigator will perform a clinical assessment. An evaluation will be done whether the patient appears to be clinically improved, unchanged, or deteriorated. The presented numbers show the percentage of patients. | Treated Set | Posted | Number | percentage of participants | From first administration of volasertib to the last dose, up to 527 days |
|
|
|
| Secondary | Vital Signs (Blood Pressure) | This endpoint will be presented as a change from baseline at last observation of systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeter of mercury (mmHg) and pulse rate (PR) in beats per minute (bpm). In this outcome measure SBP and DBP are presented. | Treated Set | Posted | Mean | Standard Deviation | mmHg | Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days) |
|
|
|
| Secondary | Vital Signs (Pulse Rate) | This endpoint will be presented as a change from baseline at last observation of systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeter of mercury (mmHg) and pulse rate (PR) in beats per minute (bpm). In this outcome measure the pulse rate is presented. | Treated Set | Posted | Mean | Standard Deviation | bpm | Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days) |
|
|
|
| Secondary | ECG | This endpoint will be presented as a change from individual baseline in QT interval, corrected according to Fridericias formula (QTcF) to end of infusion (2 hours) and 24 hours after first infusion in Cycle 1. | Treated Set, only the patients in the Maximum Tolerated Dose (MTD) groups are evaluated for this endpoint. | Posted | Mean | Standard Deviation | milliseconds (ms) | Baseline, 2 hours (before the end of infusion of volasertib) and 24 hours after first infusion in Cycle 1 |
|
|
|
| Secondary | Objective Response | The objective response (OR) was defined as complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest) assessed by tumour measurement and evaluated according to the Response Evaluation Criteria in solid tumours (RECIST), version 1.0. The data represents the percentage of patients. | The treated set | Posted | Number | percentage of patients | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
|
|
|
| Secondary | Progression-free Survival | Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. PFS was assessed by tumour measurement and evaluated according to RECIST, version 1.0. | The treated set | Posted | Median | Full Range | days | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
|
|
|
| Secondary | Response Duration | The duration of overall response was measured from the time measurement criteria were met for complete response (CR) or partial response (PR), whichever was recorded first, until the first date that recurrent or progressive disease was objectively documented. The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. | The reason not to analyze the duration of objective response is that only 2 patients in different arms achieved an objective response and the analysis would reduce to a single patient case report. | Posted | From first drug administration up to at 3 month interval after final End of treatment visit until disease progression, death, or lost to follow-up, up to 548 days |
|
|
| Secondary | Disease Control | The disease control (DC) presented are the percentage of patients with CR, PR or stable disease as best response throughout the study assessed by tumour measurement and evaluated according to RECIST, version 1.0. | The treated set | Posted | Number | percentage of patients | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
|
|
|
| Secondary | Sum of the Largest Diameters of Target Lesions | The individual time profile of the sum of the largest diameters of target lesions (LD) is presented graphically for each patient in the Clinical Trial Report (CTR) only. No descriptive statistics were planned. | No descriptive statistics were calculated, but the time profile of sum of largest diameter was plotted for each patient. | Posted | At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure) |
|
|
| Secondary | Pharmacokinetics (PK) AUC0-∞ of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure AUC0-∞ is presented. | Treated Set. All evaluable patients were included in the PK analyses. Patients who were considered not evaluable were not included. A patient was considered to be not evaluable if they had an important protocol violation relevant to the evaluation of PK, or they had insufficient data. | Posted | Geometric Mean | Geometric Coefficient of Variation | in nanogram*hours/millilitre (ng*h/mL) | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
|
|
|
| Secondary | Pharmacokinetics (PK) AUC0-168 of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure AUC0-168 is presented. | Treated Set. All evaluable patients were included in the PK analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | in nanogram*hours/millilitre (ng*h/mL) | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
|
|
|
| Secondary | Pharmacokinetics (PK) Cmax of Volasertib | The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure Cmax is presented. | Treated Set. All evaluable patients were included in the PK analyses. Patients who were considered not evaluable were not included. A patient was considered to be not evaluable if they had an important protocol violation relevant to the evaluation of PK, or they had insufficient data. D1 Schedule, no administration of trial drug on Day 8. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | V200 D1 | A single dose of 200 mg volasertib on Day 1 every 3-week course. | 0 | 3 | 3 | 3 |
| EG002 | V250 D1 | A single dose of 250 mg volasertib on Day 1 every 3-week course. | 2 | 6 | 6 | 6 |
| EG003 | V300 D1 | A single dose of 300 mg volasertib on Day 1 every 3-week course. | 7 | 17 | 17 | 17 |
| EG004 | V350 D1 | A single dose of 350 mg volasertib on Day 1 every 3-week course. | 1 | 3 | 3 | 3 |
| EG005 | V50 D1, D8 | A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. | 0 | 4 | 3 | 4 |
| EG006 | V100 D1, D8 | A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. | 2 | 4 | 4 | 4 |
| EG007 | V150 D1, D8 | A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. | 7 | 16 | 16 | 16 |
| EG008 | V200 D1, D8 | A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. | 2 | 3 | 3 | 3 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Device occlusion | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal wall abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Liver abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastroduodenal ulcer | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Reflux oesophagitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Device occlusion | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tenderness | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Escherichia infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Penis injury | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Electrocardiogram QRS complex abnormal | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Scrotal pain | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | 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.
| CTCAE Grade 2 |
|
| CTCAE Grade 3 |
|
| CTCAE Grade 4 |
|
| CTCAE Grade 5 |
|
| Improved |
|
| Unchanged |
|
| Deteriorated |
|
| DBP, chg from baseline at last observation |
|
| OR: yes |
|
| DC: yes |
|
| AUC0-168, 2nd infusion |
|
|
| After infusion Day 8 |
|
|