BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01121406
First received: April 13, 2010
Last updated: July 17, 2015
Last verified: July 2015
  Purpose

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)


Condition Intervention Phase
Ovarian Neoplasms
Drug: Paclitaxel
Drug: Gemcitabine
Drug: Topotecan
Drug: Pegylated liposomal doxorubicin (PLD)
Drug: BI 6727
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: From randomization until disease progression, death or study discontinuation; Up to 213 weeks ] [ Designated as safety issue: No ]

    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) [ Time Frame: From randomization until death or study discontinuation; Up to 213 weeks ] [ Designated as safety issue: No ]
    OS is defined as time from randomisation to death irrespective of the cause of the death.

  • Best Overall Response [ Time Frame: time from the date of randomisation until study completion/discontinuation; Up to 213 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: At screening and every 6 weeks thereafter (Up to 213 weeks) ] [ Designated as safety issue: No ]

    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 [ Time Frame: At screening and every 6 weeks thereafter (Up to 213 weeks ) ] [ Designated as safety issue: No ]

    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 Frame: Every 6 weeks (Up to 213 weeks ) ] [ Designated as safety issue: No ]

    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 Frame: Every 6 weeks (Up to 213 weeks ) ] [ Designated as safety issue: No ]

    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 Frame: Every 6 weeks (Up to 213 weeks ) ] [ Designated as safety issue: No ]

    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 Frame: Every 6 weeks (Up to 213 weeks ) ] [ Designated as safety issue: No ]

    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) [ Time Frame: Every 6 weeks (Up to 213 weeks) ] [ Designated as safety issue: No ]

    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 [ Time Frame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    Cmax; maximum measured concentration of BI 6727 BS in plasma

  • Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    t1/2; Terminal half-life of BI 6727 BS in plasma

  • t1/2; Terminal Half-life of CD 10899 BS in Plasma [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    t1/2; Terminal half-life of CD 10899 BS in plasma

  • MRT; Mean Residence Time of BI 6727 BS in the Body [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    MRT; Mean residence time of BI 6727 BS in the body

  • CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    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 [ Time Frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration ] [ Designated as safety issue: No ]
    Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS

  • Biomarkers and Pharmacogenetics Analysis (Optional) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    This endpoint has not been statistically analysed in the study report


Enrollment: 110
Study Start Date: April 2010
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 6727
Patients receive BI 6727 infusion every 3 weeks
Drug: BI 6727
Patients receive BI 6727 infusion every 3 weeks
Active Comparator: Cytotoxic
At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
Drug: Paclitaxel
Patients receive paclitaxel in a 4 week schedule
Drug: Gemcitabine
Patients receive gemcitabine in a 3 week schedule
Drug: Topotecan
Patients receive topotecan in 3 or 4 week schedule
Drug: Pegylated liposomal doxorubicin (PLD)
Patients receive PLD in a 4 week schedule

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

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

Exclusion criteria:

  1. Contre-indications for cytotoxic treatment according to the Summary of Product Characteristics (Arm B).
  2. Clinical evidence of active brain metastasis or leptomeningeal involvement.
  3. Other malignancy currently requiring active therapy.
  4. 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).
  5. Hypersensitivity to one of the trial drugs or the excipients.
  6. Serious illness or concomitant non- oncological disease.
  7. Systemic anticancer therapy within 4 weeks before the start of the study.
  8. Evidence of ileus sor sub ileus.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121406

Locations
Belgium
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
France
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
1230.18.3302A Boehringer Ingelheim Investigational Site
Paris, France
1230.18.3314A Boehringer Ingelheim Investigational Site
Paris Cedex 20, 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
Slovakia
1230.18.42101 Boehringer Ingelheim Investigational Site
Bratislava, Slovakia
1230.18.42103 Boehringer Ingelheim Investigational Site
Poprad, Slovakia
Spain
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
1230.18.34002 Boehringer Ingelheim Investigational Site
Madrid, Spain
1230.18.34003 Boehringer Ingelheim Investigational Site
Madrid, Spain
Sweden
1230.18.46005 Boehringer Ingelheim Investigational Site
Linköping, Sweden
1230.18.46001 Boehringer Ingelheim Investigational Site
Stockholm, Sweden
1230.18.46003 Boehringer Ingelheim Investigational Site
Uppsala, Sweden
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01121406     History of Changes
Other Study ID Numbers: 1230.18, 2009-015770-35
Study First Received: April 13, 2010
Results First Received: July 17, 2015
Last Updated: July 17, 2015
Health Authority: Belgium: Federal Agency for Medicinal and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Doxorubicin
Gemcitabine
Liposomal doxorubicin
Paclitaxel
Topotecan
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 03, 2015