AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Drug: bevacizumab [Avastin]; Drug: liposomal doxorubicin; Drug: paclitaxel; Drug: topotecan	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	361 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	AURELIA: A Multi-center, Open-label, Randomised, Two-arm Phase III Trial of the Effect on Progression Free Survival of Bevacizumab Plus Chemotherapy Versus Chemotherapy Alone in Patients With Platinum-resistant, Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study Start Date :	October 2009
Actual Primary Completion Date :	July 2014
Actual Study Completion Date :	July 2014

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 1	Drug: liposomal doxorubicin; 40mg/m2 iv every 4 weeks Drug: paclitaxel; 80mg/m2 iv on days 1, 8, 15 and 22 of each 4-week cycle Drug: topotecan; 4mg/m2 iv on days 1, 8 and 15 of each 4-week cycle, or 1.25 mg/kg on days 1-5 of each 3-week cycle
Experimental: 2	Drug: bevacizumab [Avastin]; 10m/kg iv every 2 weeks or 15mg/kg iv every 3 weeks Drug: liposomal doxorubicin; 40mg/m2 iv every 4 weeks Drug: paclitaxel; 80mg/m2 iv on days 1, 8, 15 and 22 of each 4-week cycle Drug: topotecan; 4mg/m2 iv on days 1, 8 and 15 of each 4-week cycle, or 1.25 mg/kg on days 1-5 of each 3-week cycle

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Disease Progression or Death (Data Cutoff 14 November 2011) [ Time Frame: 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.
2. Progression Free Survival (PFS; Data Cutoff 14 November 2011) [ Time Frame: 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 :

1. 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) [ Time Frame: 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.
2. Duration of Objective Response (Data Cutoff 14 November 2011) [ Time Frame: 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.
3. Percentage of Participants Who Died (Data Cutoff 25 January 2013) [ Time Frame: 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 ]
4. Overall Survival (Data Cutoff 25 January 2013) [ Time Frame: 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.
5. 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) [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• non-epithelial tumours
• ovarian tumours with low malignant potential
• previous treatment with >2 chemotherapy regimens
• prior radiotherapy to the pelvis or abdomen

Contacts and Locations

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Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roncolato FT, Gibbs E, Lee CK, Asher R, Davies LC, Gebski VJ, Friedlander M, Hilpert F, Wenzel L, Stockler MR, King M, Pujade-Lauraine E. Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy. Ann Oncol. 2017 Aug 1;28(8):1849-1855. doi: 10.1093/annonc/mdx229.

Bamias A, Gibbs E, Khoon Lee C, Davies L, Dimopoulos M, Zagouri F, Veillard AS, Kosse J, Santaballa A, Mirza MR, Tabaro G, Vergote I, Bloemendal H, Lykka M, Floquet A, Gebski V, Pujade-Lauraine E. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann Oncol. 2017 Aug 1;28(8):1842-1848. doi: 10.1093/annonc/mdx228.

Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. doi: 10.1016/j.ygyno.2016.11.006. Epub 2016 Nov 18.

Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16. doi: 10.1200/JCO.2013.51.4240. Epub 2014 Mar 31.

Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. doi: 10.1200/JCO.2013.51.4489. Epub 2014 Mar 17. Erratum in: J Clin Oncol. 2014 Dec 10;32(35):4025.

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00976911 History of Changes
Other Study ID Numbers:	MO22224; 2009-011400-33
First Posted:	September 15, 2009
Results First Posted:	February 25, 2015
Last Update Posted:	February 25, 2015
Last Verified:	February 2015

Additional relevant MeSH terms:

Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Bevacizumab; Liposomal doxorubicin; Doxorubicin	Topotecan; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Topoisomerase I Inhibitors