BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer | NCT01121406

ID	Type	Description	Link
2009-015770-35	EudraCT Number	EudraCT

Label	Type	Description	Intervention Names
BI 6727	Experimental	Patients receive BI 6727 infusion every 3 weeks	Drug: BI 6727
Cytotoxic	Active Comparator	At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin	Drug: Paclitaxel Drug: Gemcitabine Drug: Topotecan Drug: Pegylated liposomal doxorubicin (PLD)

Name	Type	Description	Arm Group Labels	Other Names
Paclitaxel	Drug	Patients receive paclitaxel in a 4 week schedule	Cytotoxic

Measure	Description	Time Frame
Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1	DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).	Week 24

Measure	Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival of a patient was based on the investigator's assessment; it was defined as the number of days from the date of randomisation until the date of either disease progression or death from any cause, whichever occurred first. Definition of disease progression according to RECIST version 1.1; Patients with measurable tumour lesions at baseline, Target-lesions: at least a 20% increase in the sum of diameters of target lesions, the sum of diameters must also demonstrate an absolute increase of at least 5 mm,taking as reference the smallest sum on study, or appearance of 1 or more new lesions. Non-target lesions: unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions Patients with non-measurable tumour lesions at baseline, Non-target lesions: requires unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1230.18.32003 Boehringer Ingelheim Investigational Site		Brussels			Belgium
1230.18.32004 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
37407274	Derived	Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.
26755507	Derived	Pujade-Lauraine E, Selle F, Weber B, Ray-Coquard IL, Vergote I, Sufliarsky J, Del Campo JM, Lortholary A, Lesoin A, Follana P, Freyer G, Pardo B, Vidal L, Tholander B, Gladieff L, Sassi M, Garin-Chesa P, Nazabadioko S, Marzin K, Pilz K, Joly F. Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study. J Clin Oncol. 2016 Mar 1;34(7):706-13. doi: 10.1200/JCO.2015.62.1474. Epub 2016 Jan 11.

ID	Title	Description
FG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

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

Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1

DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Units	Counts
Participants	OG00054 OG00155

Title

Denominators

Categories

Title	Measurements
	OG00030.6(18.0 to 43.2) OG00143.1(29.5 to 56.7)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Kaplan Meier estimates and confidence intervals (CI) were calculated using Greenwood's variance estimate within each treatment arm and the asymptotic CI for the difference in the rates found. The time was censored in those cases where there was no death or progression until the last trial visit					Difference in Kaplan-Meier DC rates	-12.5			2-Sided	95	-31.1	6.0			95% CI using Greenwood´s variance estimate. Volasertib (BI 6727) minus Cytotoxic.	No	Superiority or Other

Secondary

Progression Free Survival (PFS)

Progression-free survival of a patient was based on the investigator's assessment; it was defined as the number of days from the date of randomisation until the date of either disease progression or death from any cause, whichever occurred first.

Definition of disease progression according to RECIST version 1.1; Patients with measurable tumour lesions at baseline, Target-lesions: at least a 20% increase in the sum of diameters of target lesions, the sum of diameters must also demonstrate an absolute increase of at least 5 mm,taking as reference the smallest sum on study, or appearance of 1 or more new lesions.

Non-target lesions: unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions Patients with non-measurable tumour lesions at baseline, Non-target lesions: requires unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions

Posted

Median

Inter-Quartile Range

weeks

From randomization until disease progression, death or study discontinuation; Up to 213 weeks

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic

Secondary

Overall Survival (OS)

OS is defined as time from randomisation to death irrespective of the cause of the death.

Posted

Median

Inter-Quartile Range

weeks

From randomization until death or study discontinuation; Up to 213 weeks

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Best Overall Response

Best overall response (BOR) is defined as the best response recorded at any time from the date of randomisation until the end of treatment.

Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.

Posted

Number

participants

time from the date of randomisation until study completion/discontinuation; Up to 213 weeks

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria

Patients were to have a pre-treatment CA-125 of at least twice the upper limit of normal to be considered for CA-125 response. Patients were not evaluable by CA-125 if they had received mouse antibodies or if they had undergone medical and/or surgical interference with their peritoneum or pleura during the previous 28 days. In eligible patients, a CA-125 response was defined as the moment the CA- 25 was reduced by 50%, with this being confirmed with a consecutive CA-125 assessment not earlier than 28 days after the previous one.

Biological response rate based on serum CA-125 levels was assessed according to the guidelines by the Gynaecologic Cancer Intergroup. Monitoring of blood levels of the tumour marker CA-125 was performed at screening and every 6 weeks thereafter.

Posted

Number

participants

At screening and every 6 weeks thereafter (Up to 213 weeks)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic

Secondary

Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria

Biological PFS including assessment of CA-125 levels was defined as the time from randomisation until the first occurrence of progressive disease according to CA-125, progressive disease according to radiological evidence, or death.

Also according to the below criterias,

In patients with radiological measurable disease, disease progression during study treatment could not be declared on the basis of CA-125 alone.
Patients with elevated CA-125 pre-treatment and normalization of CA-125 had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart or
Patients with elevated CA-125 pre-treatment, which never normalized, had to show evidence of CA-125 ≥ to two times the nadir value on two occasions at least one week apart or
Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart.

Posted

Median

Inter-Quartile Range

weeks

At screening and every 6 weeks thereafter (Up to 213 weeks )

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Secondary

Time to Deterioration in Global Health Status/Quality of Life (QOL)

Time to deterioration in global health status/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Posted

Median

Inter-Quartile Range

weeks

Every 6 weeks (Up to 213 weeks )

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Time to Deterioration in Fatigue/Quality of Life (QOL)

Time to deterioration in fatigue/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

Posted

Median

Inter-Quartile Range

weeks

Every 6 weeks (Up to 213 weeks )

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Time to Deterioration in Pain/ Quality of Life (QOL)

Time to deterioration in pain/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

Posted

Median

Inter-Quartile Range

weeks

Every 6 weeks (Up to 213 weeks )

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL)

Time to deterioration in abdominal bloating/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

Posted

Median

Inter-Quartile Range

weeks

Every 6 weeks (Up to 213 weeks )

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL)

Three most troublesome disease specific symptoms, defined by the patient at baseline.

Patients that have defined more than 3 most troublesome symptoms have not been taken into account in the analysis.

Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

Posted

Median

Inter-Quartile Range

weeks

Every 6 weeks (Up to 213 weeks)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

Incidence and intensity of adverse events according to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Posted

Number

participants

From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

Clinically Relevant Changes in Laboratory and ECG Data

Clinically relevant changes in laboratory and ECG data

Posted

Number

percentage of participants

From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Secondary

AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS

AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for BI 6727 BS

All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS

AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for CD 10899 BS (metabolite of Volasertib BI 6727)

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS

AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for BI 6727 BS

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS

AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for CD 10899 BS (metabolite of Volasertib BI 6727)

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma

Cmax; maximum measured concentration of BI 6727 BS in plasma

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma

Cmax; maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma

tmax; time from dosing to maximum measured concentration of BI 6727 BS in plasma

Posted

Median

Full Range

hours

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma

tmax; time from dosing to maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma

Posted

Median

Full Range

hours

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

t1/2; Terminal Half-life of BI 6727 BS in Plasma

t1/2; Terminal half-life of BI 6727 BS in plasma

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

t1/2; Terminal Half-life of CD 10899 BS in Plasma

t1/2; Terminal half-life of CD 10899 BS in plasma

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

MRT; Mean Residence Time of BI 6727 BS in the Body

MRT; Mean residence time of BI 6727 BS in the body

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration

CL; total clearance of BI 6727 BS in plasma after intravenous administration

Posted

Geometric Mean

Geometric Coefficient of Variation

mL/min

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS

Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS

Posted

Geometric Mean

Geometric Coefficient of Variation

Litres

-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

ID	Title	Description
OG000	Volasertib	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.

Units	Counts
Participants	OG000

Secondary

Biomarkers and Pharmacogenetics Analysis (Optional)

This endpoint has not been statistically analysed in the study report

Posted

6 months

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
OG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Neutropenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0022 affected24 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Atrial fibrillation	Cardiac disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Abdominal distension	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Abdominal pain	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0011 affected55 at risk EG0022 affected24 at risk
Abdominal pain upper	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Ascites	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Constipation	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Ileal perforation	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Ileus	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Intestinal obstruction	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0021 affected24 at risk
Large intestine perforation	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Nausea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Rectal haemorrhage	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Small intestinal obstruction	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Subileus	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Vomiting	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Chest pain	General disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Condition aggravated	General disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Death	General disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Euthanasia	General disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
General physical health deterioration	General disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Multi-organ failure	General disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Obstruction	General disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Pyrexia	General disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Cholecystitis	Hepatobiliary disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Drug hypersensitivity	Immune system disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Device related sepsis	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Pneumonia	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Pyelonephritis	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Sepsis	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk EG0021 affected24 at risk
Urinary tract infection	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Blood alkaline phosphatase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Blood creatinine increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Gamma-glutamyltransferase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Neutrophil count decreased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Decreased appetite	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Dehydration	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Metastases to heart	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0021 affected24 at risk
Tumour invasion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Cerebrovascular accident	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Anxiety	Psychiatric disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Panic reaction	Psychiatric disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Pyelocaliectasis	Renal and urinary disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0010 affected55 at risk EG0021 affected24 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk EG0021 affected24 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Hypertension	Vascular disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk
Poor venous access	Vascular disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0020 affected24 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG00029 affected54 at risk EG00120 affected55 at risk EG0025 affected24 at risk
Leukopenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG00015 affected54 at risk EG0018 affected55 at risk EG0022 affected24 at risk
Lymphopenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG0007 affected54 at risk EG0018 affected55 at risk EG0020 affected24 at risk
Neutropenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG00034 affected54 at risk EG00117 affected55 at risk EG0027 affected24 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MEDDRA 17.0	Systematic Assessment	EG00026 affected54 at risk EG0014 affected55 at risk EG0024 affected24 at risk
Abdominal distension	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Abdominal pain	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG00013 affected54 at risk EG00120 affected55 at risk EG0025 affected24 at risk
Abdominal pain upper	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0006 affected54 at risk EG0017 affected55 at risk EG0023 affected24 at risk
Ascites	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0022 affected24 at risk
Constipation	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG00016 affected54 at risk EG00113 affected55 at risk EG0025 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG00015 affected54 at risk EG00112 affected55 at risk EG0022 affected24 at risk
Dyspepsia	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0006 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Intestinal obstruction	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Nausea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG00019 affected54 at risk EG00125 affected55 at risk EG0025 affected24 at risk
Rectal haemorrhage	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk EG0021 affected24 at risk
Stomatitis	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Vomiting	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG00015 affected54 at risk EG00118 affected55 at risk EG0022 affected24 at risk
Asthenia	General disorders	MEDDRA 17.0	Systematic Assessment	EG00018 affected54 at risk EG00126 affected55 at risk EG0024 affected24 at risk
Chest pain	General disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk EG0021 affected24 at risk
Fatigue	General disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG00112 affected55 at risk EG0024 affected24 at risk
Mucosal inflammation	General disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0017 affected55 at risk EG0021 affected24 at risk
Oedema peripheral	General disorders	MEDDRA 17.0	Systematic Assessment	EG0008 affected54 at risk EG0015 affected55 at risk EG0023 affected24 at risk
Pain	General disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0014 affected55 at risk EG0021 affected24 at risk
Pyrexia	General disorders	MEDDRA 17.0	Systematic Assessment	EG0005 affected54 at risk EG0014 affected55 at risk EG0024 affected24 at risk
Hypersensitivity	Immune system disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk EG0022 affected24 at risk
Nasopharyngitis	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk EG0021 affected24 at risk
Rhinitis	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Urinary tract infection	Infections and infestations	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0015 affected55 at risk EG0020 affected24 at risk
Alanine aminotransferase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0015 affected55 at risk EG0021 affected24 at risk
Aspartate aminotransferase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0013 affected55 at risk EG0021 affected24 at risk
Blood alkaline phosphatase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0017 affected55 at risk EG0022 affected24 at risk
Blood creatinine increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Blood uric acid increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Gamma-glutamyltransferase increased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0021 affected24 at risk
Platelet count decreased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0005 affected54 at risk EG0010 affected55 at risk EG0022 affected24 at risk
Weight decreased	Investigations	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk EG0020 affected24 at risk
Decreased appetite	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG00011 affected54 at risk EG00114 affected55 at risk EG0021 affected24 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0015 affected55 at risk EG0020 affected24 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk EG0020 affected24 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Hypokalaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0007 affected54 at risk EG0012 affected55 at risk EG0021 affected24 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0014 affected55 at risk EG0021 affected24 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0014 affected55 at risk EG0022 affected24 at risk
Back pain	Musculoskeletal and connective tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0007 affected54 at risk EG0017 affected55 at risk EG0022 affected24 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk EG0022 affected24 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0015 affected55 at risk EG0021 affected24 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk EG0023 affected24 at risk
Dysgeusia	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Headache	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0008 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Neuropathy peripheral	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0018 affected55 at risk EG0020 affected24 at risk
Paraesthesia	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0003 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Peripheral sensory neuropathy	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Anxiety	Psychiatric disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0014 affected55 at risk EG0021 affected24 at risk
Depression	Psychiatric disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk EG0021 affected24 at risk
Insomnia	Psychiatric disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0014 affected55 at risk EG0022 affected24 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0008 affected54 at risk EG0014 affected55 at risk EG0021 affected24 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0015 affected55 at risk EG0020 affected24 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0004 affected54 at risk EG0015 affected55 at risk EG0021 affected24 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk EG0020 affected24 at risk
Alopecia	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG00016 affected54 at risk EG00112 affected55 at risk EG0024 affected24 at risk
Erythema	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Hair colour changes	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk EG0022 affected24 at risk
Nail toxicity	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0014 affected55 at risk EG0020 affected24 at risk
Rash	Skin and subcutaneous tissue disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected54 at risk EG0016 affected55 at risk EG0020 affected24 at risk

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D002166	Camptothecin
D000470	Alkaloids

ID	Title	Description
BG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.
BG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Volasertib (BI 6727)	Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	24	54	53	54
EG001	Cytotoxic	Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	19	55	53	55
EG002	Cytotoxic to Volasertib Switch	Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).	12	24	21	24

ID	Term
D017239	Paclitaxel
D000093542	Gemcitabine
D019772	Topotecan
C506643	liposomal doxorubicin
C541363	BI 6727