AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT00976911
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, open-label, 2-arm study will evaluate the efficacy and safety of Avastin added to chemotherapy versus chemotherapy alone in patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with disease progression within 6 months of platinum therapy. All patients will receive standard chemotherapy with either paclitaxel or topotecan or liposomal doxorubicin. Patients randomized to Arm 2 of the study will receive Avastin (10 mg/kg iv 2-weekly or 15 mg/kg iv 3-weekly) concomitantly. Anticipated time on study treatment is until disease progression. Patients will then receive standard of care, those in Arm 1 (chemotherapy only) may opt to receive Avastin (15 mg/kg iv 3-weekly). Target sample size is 100-500 individuals.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 361
- female patients, >/=18 years of age
- epithelial ovarian, fallopian tube or primary peritoneal cancer
- platinum-resistant disease (disease progression within <6 months of platinum therapy)
- EOCG performance status of 0-2
- non-epithelial tumours
- ovarian tumours with low malignant potential
- previous treatment with >2 chemotherapy regimens
- prior radiotherapy to the pelvis or abdomen
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy liposomal doxorubicin Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m\^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks \[q3w\]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m\^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Chemotherapy + Bevacizumab liposomal doxorubicin Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated. Chemotherapy paclitaxel Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m\^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks \[q3w\]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m\^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Chemotherapy topotecan Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m\^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks \[q3w\]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m\^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Chemotherapy + Bevacizumab Bevacizumab Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated. Chemotherapy + Bevacizumab paclitaxel Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated. Chemotherapy + Bevacizumab topotecan Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Disease Progression or Death (Data Cutoff 14 November 2011) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011 Progression free survival was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurs first. Progression was based on tumour assessment made by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted.
Progression Free Survival (PFS; Data Cutoff 14 November 2011) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011 PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigators according to the RECIST criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted. Time from randomization to occurrence of disease progression or death was measured in months. An event was defined as the earliest progressive disease or death that occurred on or before the cutoff date (14 November 2011), regardless of start of nonprotocol specified anti-cancer therapy or the bevacizumab monotherapy. Disease progression was assessed by investigator according to RECIST or by symptom deterioration, and could not be declared on the basis of rising cancer antigen 125 (CA125) levels alone. Kaplan-Meier methodology was used. 95% CI for median was computed using the method of Brookmeyer and Crowley.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Best Overall Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) Per Modified RECIST (Data Cutoff 14 November 2011) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011 Objective Response was determined by the investigator using modified RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR defined as complete disappearance of all target and non-target lesions and no new lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. 95% CI computed using the normal approximation to the binomial distribution.
Duration of Objective Response (Data Cutoff 14 November 2011) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011 For randomized participants who achieved an objective response per modified RECIST, duration of objective response was defined as the time from the date of the first occurrence of a CR or PR (whichever occurred first) until the date that progressive disease or death was documented (whichever occurred first). Participants who had an objective response and did not experience disease progression or death by the time of analysis were censored at the time of the last tumor assessment. Summaries of duration of objective response (median and percentiles) were estimated from Kaplan-Meier curves. 95% CI for duration of objective response was computed using the method of Brookmeyer and Crowley.
Percentage of Participants Who Died (Data Cutoff 25 January 2013) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013 Overall Survival (Data Cutoff 25 January 2013) Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013 Duration of overall survival was defined as the time from randomization to death of any cause. Kaplan-Meier methodology was used. The OS data for participants for whom no death was captured in the clinical database were censored at the last time they were known to be alive. 95% CI was computed using the method of Brookmeyer and Crowley.
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Baseline and Weeks 8, 9, 16, 18, 24 and 30 (Data Cutoff 14 November 2011) The EORTC OV-28 module is a questionnaire that focuses on issues specific to ovarian cancer. It assesses AB/GI symptoms, among others. Participants were asked to indicate the extent to which they experienced AB/GI symptoms in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen/stomach? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms). Participants were considered a responder if they had a 10 point or more reduction in EORTC QLQ-OV28 AB/GI symptom scale score from baseline.
Trial Locations
- Locations (117)
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Clinique Ste-Elisabeth
🇧🇪Namur, Belgium
University Clinical Centre of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Clinic of Oncology, University Clinical Center Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
University Clinical Center Tuzla; Clinic for Gynecology and Obstetrition
🇧🇦Tuzla, Bosnia and Herzegovina
Herlev Hospital; Afdeling for Kræftbehandling
🇩🇰Herlev, Denmark
Regionshospitalet Herning; Onkologisk afdeling
🇩🇰Herning, Denmark
Rigshospitalet; Onkologisk Klinik
🇩🇰København Ø, Denmark
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