BI 6727

Boehringer Ingelheim

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.

Dose Finding Study of BI 6727 (Volasertib) in Patients With Various Solid Cancers

A Phase I Single Dose Escalation Study of Two Dosing Schedules of BI 6727 Administered Intravenously in Asian Patients With Various Solid Cancers With Repeated Administration in Patients With Clinical Benefit

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.

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.

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.

This endpoint will be presented as a 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 neutrophils.

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.

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.

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.

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.

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.

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 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 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 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.

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.

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.

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.

A single dose of 100 mg volasertib on Day 1 every 3-week course.

V100 D1

A single dose of 200 mg volasertib on Day 1 every 3-week course.

V200 D1

A single dose of 250 mg volasertib on Day 1 every 3-week course.

V250 D1

A single dose of 300 mg volasertib on Day 1 every 3-week course.

V300 D1

A single dose of 350 mg volasertib on Day 1 every 3-week course.

V350 D1

A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.

V50 D1, D8

A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.

V100 D1, D8

A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.

V150 D1, D8

A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.

V200 D1, D8

Total

Age, Continuous

Sex: Female, Male

The treated set consisted of all patients who received at least one dose of volasertib.

Boehringer Ingelheim, Call Center

The treated set consisted of all patients whe received at least one dose of volasertib.

Percentage of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib

A single dose of volasertib on Day 1 every 3-week course.

Volasertib D1 Schedule

A single dose of volasertib on Day 1 and Day 8 every 3-week course.

Volasertib D1 and D 8 Schedule

MTD of Volasertib

CTCAE Grade 1

CTCAE Grade 2

CTCAE Grade 3

CTCAE Grade 4

CTCAE Grade 5

Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0

Change From Baseline to Last Value on Treatment in Platelets

Change From Baseline to Last Value on Treatment in Neutrophils

Unknown

Improved

Unchanged

Deteriorated

Patient Performance

SBP, chg from baseline at last observation

DBP, chg from baseline at last observation

Vital Signs (Blood Pressure)

Vital Signs (Pulse Rate)

Change from baseline after 2 hours

Change from baseline after 24 hours

Treated Set, only the patients in the Maximum Tolerated Dose (MTD) groups are evaluated for this endpoint.

OR: no or unknown

OR: yes

Objective Response

Progression-free Survival

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.

Response Duration

DC: no or unknown

DC: yes

Disease Control

No descriptive statistics were calculated, but the time profile of sum of largest diameter was plotted for each patient.

Sum of the Largest Diameters of Target Lesions

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.

Pharmacokinetics (PK) AUC0-∞ of Volasertib

AUC0-168, 1st infusion

AUC0-168, 2nd infusion

Treated Set. All evaluable patients were included in the PK analyses.

Pharmacokinetics (PK) AUC0-168 of Volasertib

After infusion Day 1

After infusion Day 8

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.

Pharmacokinetics (PK) Cmax of Volasertib

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.).

V 100 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.

V 200 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.

V 250 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.

V 300 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.

V 350 mg D1

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.

V 50 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.

V 100 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.

V 150 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.

Spots Global Cancer Trial Database for Dose Finding Study of BI 6727 (Volasertib) in Patients With Various Solid Cancers

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