Clinical trial NCT01121406: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-05-12
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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.

Primary outcomes:
measure: Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
timeFrame: Week 24
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization until disease progression, death or study discontinuation; Up to 213 weeks
measure: Overall Survival (OS)
timeFrame: From randomization until death or study discontinuation; Up to 213 weeks
measure: Best Overall Response
timeFrame: time from the date of randomisation until study completion/discontinuation; Up to 213 weeks
measure: Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria
timeFrame: At screening and every 6 weeks thereafter (Up to 213 weeks)
measure: Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria
timeFrame: At screening and every 6 weeks thereafter (Up to 213 weeks )
measure: Time to Deterioration in Global Health Status/Quality of Life (QOL)
timeFrame: Every 6 weeks (Up to 213 weeks )
measure: Time to Deterioration in Fatigue/Quality of Life (QOL)
timeFrame: Every 6 weeks (Up to 213 weeks )
measure: Time to Deterioration in Pain/ Quality of Life (QOL)
timeFrame: Every 6 weeks (Up to 213 weeks )
measure: Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL)
timeFrame: Every 6 weeks (Up to 213 weeks )
measure: Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL)
timeFrame: Every 6 weeks (Up to 213 weeks)
measure: 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
timeFrame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
measure: Clinically Relevant Changes in Laboratory and ECG Data
timeFrame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
measure: AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: t1/2; Terminal Half-life of BI 6727 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: t1/2; Terminal Half-life of CD 10899 BS in Plasma
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: MRT; Mean Residence Time of BI 6727 BS in the Body
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS
timeFrame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
measure: Biomarkers and Pharmacogenetics Analysis (Optional)
timeFrame: 6 months
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: 1230.18.32003 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1230.18.32004 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1230.18.32002 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1230.18.32001 Boehringer Ingelheim Investigational Site
city: Angers Cedex 9
country: France
facility: 1230.18.3321A Boehringer Ingelheim Investigational Site
city: Bordeaux cedex
country: France
facility: 1230.18.3307A Boehringer Ingelheim Investigational Site
city: Caen
country: France
facility: 1230.18.3301A Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 1230.18.3322A Boehringer Ingelheim Investigational Site
city: Lyon
country: France
facility: 1230.18.3313A Boehringer Ingelheim Investigational Site
city: Nantes cedex 02
country: France
facility: 1230.18.3312A Boehringer Ingelheim Investigational Site
city: Nice cedex
country: France
facility: 1230.18.3308A Boehringer Ingelheim Investigational Site
city: Paris Cedex 20
country: France
facility: 1230.18.3314A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1230.18.3302A Boehringer Ingelheim Investigational Site
city: Pierre-Bénite cedex
country: France
facility: 1230.18.3309A Boehringer Ingelheim Investigational Site
city: Reims cedex
country: France
facility: 1230.18.3305A Boehringer Ingelheim Investigational Site
city: Saint-Brieuc cedex
country: France
facility: 1230.18.3320A Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 1230.18.3311A Boehringer Ingelheim Investigational Site
city: Toulouse Cedex 9
country: France
facility: 1230.18.3310A Boehringer Ingelheim Investigational Site
city: Vandoeuvre les Nancy cedex
country: France
facility: 1230.18.3315A Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 1230.18.42101 Boehringer Ingelheim Investigational Site
city: Poprad
country: Slovakia
facility: 1230.18.42103 Boehringer Ingelheim Investigational Site
city: Badalona
country: Spain
facility: 1230.18.34006 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1230.18.34001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1230.18.34005 Boehringer Ingelheim Investigational Site
city: Girona
country: Spain
facility: 1230.18.34007 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: 1230.18.34004 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1230.18.34002 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1230.18.34003 Boehringer Ingelheim Investigational Site
city: Linköping
country: Sweden
facility: 1230.18.46005 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1230.18.46001 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 1230.18.46003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.