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BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer

Primary Purpose

Ovarian Neoplasms

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Paclitaxel

Gemcitabine

Topotecan

Pegylated liposomal doxorubicin (PLD)

BI 6727

About this trial

This is an interventional treatment trial for Ovarian Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

Confirmed recurrent epithelial ovarian carcinoma, peritoneal carcinoma or fallopian tube carcinoma.
Platinum resistant or platinum refractory disease.
Eastern Collaborative Oncology Group performance status < = 2.
Life expectancy > = 3 months.
At least one measurable lesion (Response Evaluation Criteria In Solid Tumours version 1.1).
Adequate hepatic, renal and bone marrow functions.
signed written informed consent prior to admission to the study.

Exclusion criteria:

Contre-indications for cytotoxic treatment according to the Summary of Product Characteristics (Arm B).
Clinical evidence of active brain metastasis or leptomeningeal involvement.
Other malignancy currently requiring active therapy.
QTc prolongation according to Fridericia formula deemed clinically relevant by the investigator (e.g., congenital long QT syndrome, QTc according to Fridericia formula > 470 ms).
Hypersensitivity to one of the trial drugs or the excipients.
Serious illness or concomitant non- oncological disease.
Systemic anticancer therapy within 4 weeks before the start of the study.
Evidence of ileus sor sub ileus.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BI 6727

Cytotoxic

Arm Description

Patients receive BI 6727 infusion every 3 weeks

At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Overall Survival (OS)

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

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.

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.

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.

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.

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. 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.

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. 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.

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. 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.

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. 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.

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

Clinically Relevant Changes in Laboratory and ECG Data

Clinically relevant changes in laboratory and ECG data

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

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)

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

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)

Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma

Cmax; maximum measured concentration of BI 6727 BS in plasma

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

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

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

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

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

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

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

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

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

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

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

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

Biomarkers and Pharmacogenetics Analysis (Optional)

This endpoint has not been statistically analysed in the study report

Full Information

NCT ID

NCT01121406

First Posted

April 13, 2010

Last Updated

July 17, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01121406

Brief Title

BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer

Official Title

Phase II Randomized Trial of the Polo-like Kinase 1 Inhibitor BI 6727 Monotherapy Versus Investigator´s Choice Chemotherapy in Ovarian Cancer Patients Resistant or Refractory to Platinum-based Cytotoxic Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

April 2010 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

This is an international, randomized phase II trial. The aim is to assess the efficacy and the safety of BI 6727 Versus investigator's best choice single agent cytotoxic in recurrent third and fourth lines platinum resistant/refractory ovarian cancer. 100 patients will be randomised at the study entry to receive either BI 6727 (Arm A: 50 patients) or non-platinum single agent cytotoxic (Arm B: 50 patients) Treatment will be continued until disease progression or unacceptable toxicity. Primary endpoint: disease control rate at week 24 according to Response Evaluation Criteria In Solid Tumours version 1.1. Secondary endpoints: efficacy (progression free survival, overall survival, biological tumour response, biological progression free survival assessed by serum CA 125 according to Gynecologic Cancer Intergroup criteria, safety according to the NCI CTCAE v.3, disease symptoms control assessed by the EORTC QLQ-C30, QLQ-OV28 and individual symptoms questionnaires, pharmacokinetics of BI 6727. Others endpoints: biomarkers and pharmacogenetics analysis (optional)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BI 6727

Arm Type

Experimental

Arm Description

Patients receive BI 6727 infusion every 3 weeks

Arm Title

Cytotoxic

Arm Type

Active Comparator

Arm Description

At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Intervention Description

Patients receive paclitaxel in a 4 week schedule

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Patients receive gemcitabine in a 3 week schedule

Intervention Type

Drug

Intervention Name(s)

Topotecan

Intervention Description

Patients receive topotecan in 3 or 4 week schedule

Intervention Type

Drug

Intervention Name(s)

Pegylated liposomal doxorubicin (PLD)

Intervention Description

Patients receive PLD in a 4 week schedule

Intervention Type

Drug

Intervention Name(s)

BI 6727

Intervention Description

Patients receive BI 6727 infusion every 3 weeks

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

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

Title

Overall Survival (OS)

Description

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

Time Frame

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

Title

Best Overall Response

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Every 6 weeks (Up to 213 weeks )

Title

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

Description

Time Frame

Every 6 weeks (Up to 213 weeks )

Title

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

Description

Time Frame

Every 6 weeks (Up to 213 weeks )

Title

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

Description

Time Frame

Every 6 weeks (Up to 213 weeks )

Title

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

Description

Time Frame

Every 6 weeks (Up to 213 weeks)

Title

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

Description

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

Time Frame

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

Title

Clinically Relevant Changes in Laboratory and ECG Data

Description

Clinically relevant changes in laboratory and ECG data

Time Frame

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

Title

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

Description

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

Time Frame