BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer
- Conditions
- Ovarian Neoplasms
- Interventions
- Registration Number
- NCT01121406
- Lead Sponsor
- Boehringer Ingelheim
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 110
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 6727 BI 6727 Patients receive BI 6727 infusion every 3 weeks Cytotoxic Paclitaxel At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin Cytotoxic Pegylated liposomal doxorubicin (PLD) At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin Cytotoxic Topotecan At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin Cytotoxic Gemcitabine At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
- Primary Outcome Measures
Name Time Method Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 Week 24 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
Name Time Method AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration 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-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration 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)
Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration tmax; time from dosing to maximum measured concentration of BI 6727 BS in plasma
t1/2; Terminal Half-life of CD 10899 BS in Plasma -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration t1/2; Terminal half-life of CD 10899 BS in plasma
Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS
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 From first treatment administration to 21 days after the last drug administration (Up to 1403 days) 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 From first treatment administration to 21 days after the last drug administration (Up to 1403 days) Clinically relevant changes in laboratory and ECG data
Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration Cmax; maximum measured concentration of BI 6727 BS in plasma
MRT; Mean Residence Time of BI 6727 BS in the Body -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration MRT; Mean residence time of BI 6727 BS in the body
Progression Free Survival (PFS) From randomization until disease progression, death or study discontinuation; Up to 213 weeks 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 lesionsOverall Survival (OS) From randomization until death or study discontinuation; Up to 213 weeks OS is defined as time from randomisation to death irrespective of the cause of the death.
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria At screening and every 6 weeks thereafter (Up to 213 weeks) 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 At screening and every 6 weeks thereafter (Up to 213 weeks ) 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 Pain/ Quality of Life (QOL) Every 6 weeks (Up to 213 weeks ) 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.Best Overall Response time from the date of randomisation until study completion/discontinuation; Up to 213 weeks 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.Time to Deterioration in Global Health Status/Quality of Life (QOL) Every 6 weeks (Up to 213 weeks ) 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) Every 6 weeks (Up to 213 weeks ) 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 Abdominal Bloating/ Quality of Life (QOL) Every 6 weeks (Up to 213 weeks ) 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.AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration 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)
Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration tmax; time from dosing to maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma
CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration CL; total clearance of BI 6727 BS in plasma after intravenous administration
Biomarkers and Pharmacogenetics Analysis (Optional) 6 months This endpoint has not been statistically analysed in the study report
Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL) Every 6 weeks (Up to 213 weeks) 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.AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for BI 6727 BS
Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration Cmax; 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 -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration t1/2; Terminal half-life of BI 6727 BS in plasma
Trial Locations
- Locations (31)
1230.18.32003 Boehringer Ingelheim Investigational Site
🇧🇪Brussel, Belgium
1230.18.32004 Boehringer Ingelheim Investigational Site
🇧🇪Edegem, Belgium
1230.18.32002 Boehringer Ingelheim Investigational Site
🇧🇪Gent, Belgium
1230.18.32001 Boehringer Ingelheim Investigational Site
🇧🇪Leuven, Belgium
1230.18.3321A Boehringer Ingelheim Investigational Site
🇫🇷Angers Cedex 9, France
1230.18.3307A Boehringer Ingelheim Investigational Site
🇫🇷Bordeaux cedex, France
1230.18.3301A Boehringer Ingelheim Investigational Site
🇫🇷Caen, France
1230.18.3322A Boehringer Ingelheim Investigational Site
🇫🇷Lille Cedex, France
1230.18.3313A Boehringer Ingelheim Investigational Site
🇫🇷Lyon, France
1230.18.3312A Boehringer Ingelheim Investigational Site
🇫🇷Nantes cedex 02, France
1230.18.3308A Boehringer Ingelheim Investigational Site
🇫🇷Nice cedex, France
1230.18.3314A Boehringer Ingelheim Investigational Site
🇫🇷Paris Cedex 20, France
1230.18.3302A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1230.18.3309A Boehringer Ingelheim Investigational Site
🇫🇷Pierre-Bénite cedex, France
1230.18.3305A Boehringer Ingelheim Investigational Site
🇫🇷Reims cedex, France
1230.18.3320A Boehringer Ingelheim Investigational Site
🇫🇷Saint-Brieuc cedex, France
1230.18.3311A Boehringer Ingelheim Investigational Site
🇫🇷Strasbourg, France
1230.18.3310A Boehringer Ingelheim Investigational Site
🇫🇷Toulouse Cedex 9, France
1230.18.3315A Boehringer Ingelheim Investigational Site
🇫🇷Vandoeuvre les Nancy cedex, France
1230.18.42103 Boehringer Ingelheim Investigational Site
🇸🇰Poprad, Slovakia
1230.18.34006 Boehringer Ingelheim Investigational Site
🇪🇸Badalona, Spain
1230.18.34001 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1230.18.34005 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1230.18.34007 Boehringer Ingelheim Investigational Site
🇪🇸Girona, Spain
1230.18.34004 Boehringer Ingelheim Investigational Site
🇪🇸L'Hospitalet de Llobregat, Spain
1230.18.46005 Boehringer Ingelheim Investigational Site
🇸🇪Linköping, Sweden
1230.18.34002 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1230.18.34003 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1230.18.46001 Boehringer Ingelheim Investigational Site
🇸🇪Stockholm, Sweden
1230.18.46003 Boehringer Ingelheim Investigational Site
🇸🇪Uppsala, Sweden
1230.18.42101 Boehringer Ingelheim Investigational Site
🇸🇰Bratislava, Slovakia