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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976911
• Other study ID #: MO22224
• Secondary ID: 2009-011400-33
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2009
• Est. completion date: July 9, 2014

Study information

• Verified date: May 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 361
• Est. completion date: July 9, 2014
• Est. primary completion date: July 9, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Bevacizumab
10m/kg iv every 2 weeks or 15mg/kg iv every 3 weeks
• liposomal doxorubicin
40mg/m2 iv every 4 weeks
• paclitaxel
80mg/m2 iv on days 1, 8, 15 and 22 of each 4-week cycle
• 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

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	Clinique Ste-Elisabeth	Namur
Bosnia and Herzegovina	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
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Regionshospitalet Herning; Onkologisk afdeling	Herning
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital; Gynaecology & Obstetrics Dept	Oulu
France	Clinique Sainte Catherine; Hopital De Semaine	Avignon
France	Clinique Tivoli; Sce Radiotherapie	Bordeaux
France	Institut Bergonie; Gynecologie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie	Bordeaux
France	Ch De Brive La Gaillarde; Radiotherapie Oncologie	Brive La Gaillarde
France	Centre Francois Baclesse; Urologie Gynecologie	Caen
France	Centre Jean Perrin; Hopital De Jour	Clermont Ferrand
France	Hopital Louis Pasteur; Medecine B	Colmar
France	Institut Daniel Hollard; Chimiotherapie Ambulatoire	Grenoble
France	Centre Hospitalier Departemental Les Oudairies	La Roche Sur Yon
France	Hopital La Source; Onco Med Hematologie Clinique	La Source
France	Hopital Andre Mignot; Hematologie - Oncologie	Le Chesnay
France	Centre Jean Bernard	Le Mans
France	Centre Oscar Lambret; Cancerologie Gynecologique	Lille
France	Clin Mut De Lyon Eugene Andre; Medecine 3 A	Lyon
France	Hopital Layne; Medecine Ambulatoire	Mont-de-marsan
France	Centre Val Aurelle Paul Lamarque; Medecine A1 A2	Montpellier
France	Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE	Nancy
France	Centre Catherine de Sienne; Chimiotherapie	Nantes
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	Polyclinique Kenval ; Radiotherapie Oncologie	Nimes
France	Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)	Paris
France	HOPITAL TENON; Cancerologie Medicale	Paris
France	Hotel Dieu; Hematologie- Oncologie	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Clinique Francheville; Radiotherapie	Perigueux
France	Institut Jean Godinot; Oncologie Medicale	Reims CEDEX
France	Centre Henri Becquerel; Oncologie Medicale	Rouen
France	Clinique Armoricaine Radiologie; Cons Externes	Saint Brieuc
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Centre Radiotherapie Etienne Dolet	Saint Nazaire
France	Centre Rene Huguenin; Medecine B	St Cloud
France	Hopital Civil; Expl Fonct Systeme Nerveux	Strasbourg
France	Hopitaux Du Leman Site Thonon; Maternite Gynecologie	Thonon Les Bains
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy
Germany	Campus Virchow-Klinikum Charité; Centrum 17; Klinik für Gynäkologie	Berlin
Germany	HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe	Berlin
Germany	Evangelischen Krankenhauses Düsseldorf; Frauenklinik	Düsseldorf
Germany	Uni-Frauenklinik	Düsseldorf
Germany	Universitätsklinikum Erlangen; Frauenklinik	Erlangen
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Universitätsklinikum Essen; Zentrum Für Frauenheilkunde	Essen
Germany	Klinik Johann Wolfgang von Goethe Uni; Klinik für Frauenheilkunde und Geburtshilfe	Frankfurt
Germany	Kath.Marienkrankenhaus gGmbH Frauenklinik	Hamburg
Germany	Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding	Hannover
Germany	Praxisgemeinschaft; Frauenärzte am Bahnhofsplatz	Hildesheim
Germany	Klinikum Kassel GmbH; Klinik für Frauenheilkunde und Geburtshilfe	Kassel
Germany	UNI-Klinikum Campus Kiel Klinik für Gynäkologie und Geburtshilfe	Kiel
Germany	HELIOS Klinikum Krefeld; Klinik für Frauenheilkunde und Geburtshilfe	Krefeld
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe	Lübeck
Germany	Universitätsklinikum Mannheim; Frauenklinik	Mannheim
Germany	Klinikum der Universität München; Campus Großhadern; Klinik und Poliklinik für Frauenheilkunde	Muenchen
Germany	Klinikum Nord Frauenklinik	Nürnberg
Germany	Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe	Offenbach
Germany	Oncologianova GmbH	Recklinghausen
Germany	Universitätsfrauen- und Poliklinik am Klinikum Suedstadt	Rostock
Germany	Städtisches Klinikum Solingen; Klinik für Frauenheilkunde und Geburtshilfe	Solingen
Germany	Robert-Bosch-Krankenhaus; Interdisziplinäres Zentrum; Tumorzentrum	Stuttgart
Germany	Universitätsklinik Tübingen; Frauenklinik & Poliklinik	Tübingen
Germany	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm
Germany	Dr. Horst-Schmidt-Kliniken; Frauenheilkunde & Geburtshilfe	Wiesbaden
Greece	University Hospital of Alexandra	Athens
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	Ospedali Riuniti; Divisione Ostetricia e Ginecologia	Bergamo	Lombardia
Italy	Az. Osp. Carlo Poma; Divisione Di Oncologia Medica	Mantova	Lombardia
Italy	Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica	Milano	Lombardia
Italy	AZIENDA POLICLINICO UMBERTO I; Ginecologia ed Ostetricia	Roma	Lazio
Italy	Istituto Regina Elena; Oncologia Medica A	Roma	Lazio
Italy	Ospedale S.G.Calibita Fatebenefratelli; Unità Operativa Oncologia	Roma	Lazio
Italy	A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia	Udine	Friuli-Venezia Giulia
Netherlands	Meander Mc, Locatie Lichtenberg; Dept of Lung Diseases	Amersfoort
Netherlands	Leyenburg Ziekenhuis; Internal Medecine	Den Haag
Netherlands	Catharina ZKHS; Inwendige Geneeskunde Afd.	Eindhoven
Netherlands	Martini Ziekenhuis; Dept of Internal Medicine	Groningen
Netherlands	Stichting St. Antonius Ziekenhuis	Nieuwegein
Netherlands	Universitair Medisch Centrum Utrecht; Inwendige Geneeskunde Afd.	Utrecht
Norway	The Norvegian Radium Hospital Montebello; Dept of Oncology	Oslo
Norway	St. Olavs Hospital; Kvinneklinikken	Trondheim
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital de Terrassa; Servicio de Oncologia	Barcelona
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid
Spain	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia	Murcia
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Sweden	Uni Hospital Linkoeping; Dept. of Oncology	Linköping
Sweden	Örebro University Hospital; Department of Gynecologic Oncology	Örebro
Sweden	Norrlands Uni Hospital; Onkologi Avd.	Umeå
Sweden	Akademiska sjukhuset, Onkologkliniken	Uppsala
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Ankara Baskent University Medicine Faculty; Gynaecology	Ankara
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	Anadolu Health Center; Medical Oncology	Kocaeli

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  Bosnia and Herzegovina,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Disease Progression or Death (Data Cutoff 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.	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
Primary	Progression Free Survival (PFS; Data Cutoff 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.	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
Secondary	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)	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.	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
Secondary	Duration of Objective Response (Data Cutoff 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.	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
Secondary	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
Secondary	Overall Survival (Data Cutoff 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.	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
Secondary	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)	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.	Baseline and Weeks 8, 9, 16, 18, 24 and 30 (Data Cutoff 14 November 2011)