Trial Outcomes & Findings for Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer (NCT NCT01023958)

Last Updated: 2017-11-22

Results Overview

Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

From first drug administration until end of study, up to 2 years

Results posted on

2017-11-22

Participant Flow

An open-label, single-arm, Phase II trial of intravenous volasertib (BI 6727) in patients with locally advanced, metastatic or recurrent urothelial cancer of the bladder, renal pelvis, or ureters after failure of prior chemotherapy.

Participant milestones

Participant milestones
Measure	Volasertib (BI 6727) Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Overall Study STARTED	50
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Volasertib (BI 6727) Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Overall Study Progressive disease	48
Overall Study Other adverse event	1
Overall Study Refused to continue medication	1

Baseline Characteristics

Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Age, Continuous	69.0 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first drug administration until end of study, up to 2 years

Population: TS

Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Objective Tumour Response According to RECIST Criteria	14.0 Percentage of participants Interval 5.8 to 26.7

SECONDARY outcome

Timeframe: Time from first treatment to the occurrence of tumor progression or death, up to 2 years

Population: TS

Progression-free survival (PFS) is the time from first treatment to the occurrence of tumor progression or death, whichever occurs first. Disease progression is defined according to the RECIST guideline but also includes the investigators' assessment which may, in some cases, include only clinical progression (deterioration of general health status per investigator). PFS was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals. Patients without evidence of disease progression were to be censored at the last image date.

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Progression-free Survival	6.1 Weeks Interval 5.6 to 11.1

SECONDARY outcome

Timeframe: Time from first infusion to death, up to 2 years

Population: TS

Overall survival (OS) is the time from first infusion to death. Patients who were alive at the time of analysis or lost to follow-up were censored at the last follow-up date when they were known to be alive. Overall survival was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Overall Survival	8.5 Months Interval 3.9 to 12.1

SECONDARY outcome

Timeframe: From the time of first response (CR or PR) to progression or death, up to 2 years

Population: TS

The duration of overall response is measured from the time of first response (CR or PR) to progression or death whichever occurs first.

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=7 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Duration of Overall Response	41.0 Weeks Interval 29.1 to 77.3

SECONDARY outcome

Timeframe: From first drug administration until end of study, up to 2 years

Population: TS

Disease control rate. Disease control is defined as having a best overall response of complete response (CR), partial response (PR) or stable disease (SD).

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Disease Control Rate	40.0 Percentage of participants Interval 26.4 to 54.8

SECONDARY outcome

Timeframe: Time of first response to progression or death, up to 2 years

Population: Patients who achieved disease control in the TS.

Disease control is defined as having a best overall response of CR, PR, or SD. The duration of disease control is measured from the time of first response to progression or death whichever occurs first.

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=20 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Duration of Disease Control	27.0 Weeks Interval 10.1 to 77.3

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: Pharmacokinetic set (PKS) including patients with analyzable data for this endpoint.

Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=48 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
AUC0-∞ of Volasertib	5470 ng*h/mL Geometric Coefficient of Variation 30.6

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: PKS including patients with analyzable data for this endpoint.

Maximum measured concentration in plasma (Cmax) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=47 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Cmax of Volasertib	253 ng/mL Geometric Coefficient of Variation 51.9

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: PKS including patients with analyzable data for this endpoint.

Terminal half-life (t1/2) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=48 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
t1/2 of Volasertib	150 hours Geometric Coefficient of Variation 17.0

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: PKS including patients with analyzable data for this endpoint.

Total plasma clearance after intravascular administration (CL) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=48 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
CL of Volasertib	914 mL/min Geometric Coefficient of Variation 30.6

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: PKS including patients with analyzable data for this endpoint.

Apparent volume of distribution at steady state following intravascular administration (Vss) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=48 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Vss of Volasertib	7470 Litres Geometric Coefficient of Variation 32.4

SECONDARY outcome

Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Population: PKS including patients with analyzable data for this endpoint.

Time from dosing to maximum measured concentration (Tmax) of volasertib

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=47 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Tmax of Volasertib	2.03 Hours Interval 1.53 to 4.17

SECONDARY outcome

Timeframe: From first drug administration until end of study, up to 2 years

Population: TS

Occurrence and intensity of adverse events (AEs) graded according to Common Toxicity Criteria of Adverse Events (CTCAE). The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

Outcome measures

Outcome measures
Measure	Volasertib (BI 6727) n=50 Participants Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication
Occurrence and Intensity of AE's Graded According to CTCAE Grade 1	8.0 Percentage of participants
Occurrence and Intensity of AE's Graded According to CTCAE Grade 2	28.0 Percentage of participants
Occurrence and Intensity of AE's Graded According to CTCAE Grade 3	36.0 Percentage of participants
Occurrence and Intensity of AE's Graded According to CTCAE Grade 4	20.0 Percentage of participants
Occurrence and Intensity of AE's Graded According to CTCAE Grade 5	6.0 Percentage of participants

SECONDARY outcome

Timeframe: From first drug administration up to 21 days after final administration, up to 2 years

Population: TS

Occurrence of unacceptable toxicity is defined by CTCAE as as drug related CTCAE Grade 3 or greater non-hematological toxicity (except emesis or diarrhea responding to supportive treatment); drug-related CTCAE Grade 4 neutropenia for seven or more days and / or complicated by infection; or drug-related CTCAE Grade 4 thrombocytopenia.