Clinical trial NCT01837251: Evaluation of Optimal Treatment With Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer
Official title: A Prospective Randomized Phase III Trial of Carboplatin/Gemcitabine/Bevacizumab vs. Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Platinum-sensitive Ovarian Cancer
Keywords: Ovarian Carcinoma
Bevacizumab
Gemcitabine
PLD
pegylated liposomal doxorubicin
Carboplatin
best therapeutic index
progression-free survival
Lead sponsor: AGO Research GmbH
Sponsor class: INDUSTRY
Collaborators: name: Arbeitsgemeinschaft Gynaekologische Onkologie Austria
name: ARCAGY/ GINECO GROUP
name: Australia New Zealand Gynaecological Oncology Group
name: Scottish Gynaecological Cancer Study Group
First posted: 2013-04-23
Enrollment: 682
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: Evaluation of the best therapeutic index for patients with platinum-sensitive ovarian cancer when treatment with bevacizumab and gemcitabine/carboplatin or with bevacizumab and PLD/carboplatin.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma
2. First disease recurrence \>6 months after first-line platinum-based chemotherapy
3. Patients with measurable or non-measurable disease (RECIST v1.1) or CA 125 assessable disease (GCIG criteria) or histological proven diagnosis of relapse
4. In case of cytoreductive surgery for recurrence, patients must be able to commence cytotoxic chemo-therapy within 8 weeks after cytoreductive surgery
5. ECOG PS 0-2
6. Absolute Neutrophil Count \>= 1.5 x 10\^9/L; Platelets \>= 100 x 10\^9/L; Hemoglobin \>= 9.5 g/dL
7. Patients not receiving anticoagulant medication who have an International Normalized Ratio \<= 1.5 and an Activated ProThrombin Time \<= 1.5 x ULN
8. Serum bilirubin \<= 2 x ULN; Serum transaminases \<= 2.5 x ULN (\<= 5 x ULN in the presence of liver metastasis)
9. Serum creatinine \< 1.6 mg/dL or creatinine clearance \>= 40 mL/min; Glomerular filtration rate \> 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula); Urine dipstick for proteinuria \< 2+. If urine dipstick is \>= 2+, 24 hour urine collection must demonstrate \<= 1 g of protein in 24 hours
10. Normal blood pressure or adequately treated and controlled hypertension (either systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg)

Exclusion Criteria:

1. Ovarian tumors of low malignant potential
2. Malignancies other than ovarian cancer within 5 years prior to randomization
3. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period
4. Any previous radiotherapy to the abdomen or pelvis
5. Known hypersensitivity to used chemotherapeutic agents in this trial and bevacizumab and its excipients, chinese hamster ovary cell products or other recombinant human or humanised antibodies
6. Current or recent chronic use of aspirin \> 325 mg/day
7. Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of Bevacizumab
8. History of VEGF therapy related abdominal fistula or gastrointestinal perforation
9. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease
10. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
11. Previous Cerebro-Vascular Accident , Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage
12. Prior history of hypertensive crisis or hypertensive encephalopathy
13. Clinically significant disease, including: myocardial infarction or unstable angina within ≤ 6 months of randomization; New York Heart Association (NYHA) \>= grade 2 Congestive Heart Failure; poorly controlled cardiac arrhythmia despite medication; peripheral vascular disease grade \>= 3
14. LVEF defined by ECHO/MUGA below the institutional lower limit of normal
15. Significant traumatic injury during 4 weeks prior to randomization
16. Current brain metastases or spinal cord compression
17. History or evidence upon neurological examination of central nervous system disease
18. Non-healing wound, active ulcer or bone fracture
19. History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
20. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic coagulation)
21. Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the duration of the trial and at least 6 months afterwards
22. Pregnant or lactating women
23. Requirement of therapeutic anticoagulation using marcumar, warfarin or PTT-prolonging heparin

Primary outcomes:
measure: investigator-determined progression-free survival
timeFrame: every 12 weeks until progression or up to 30 months (whichever occurs first)
Secondary outcomes:
measure: biological progression-free survival by serum CA 125
timeFrame: every 3 weeks until progression or up to 30 months (whichever occurs first)
measure: Health related Quality of Life (QoL)
timeFrame: Baseline and then every 12 weeks until investigator-determined progresssion-free survival and thereafter at every visit for th 5-years follow-up or death (whichever occurs first)
measure: Safety and Tolerability, i.e. type, frequency, severity and duration o adverse reactions
timeFrame: every 3 weeks, 30 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later)
measure: Overall Survival
timeFrame: every 3 weeks during treatment with bevacizumab, thereafter every 6 months; for up 30 months
Other outcomes:
Locations:
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe Hospital
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Coffs Harbour
country: Australia
facility: NCCI - Coffs Harbour Hospital
city: Douglas
country: Australia
facility: The Townsville Hospital
city: Frankston
country: Australia
facility: Peninsula Health - Frankston Hospital
city: Geelong
country: Australia
facility: Andrew Love Cancer Centre Geelong
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Kogarah
country: Australia
facility: St. George Hospital
city: Milton
country: Australia
facility: ICON Cancer Care Centre
city: Nambour
country: Australia
facility: Nambour General Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner
city: Port Macquarie
country: Australia
facility: North Coast Cancer Institute
city: Randwick
country: Australia
facility: Royal Hospital for Women
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: Southport
country: Australia
facility: Gold Coast University Hospital
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
city: Subiaco
country: Australia
facility: St. John of God Hospital
city: Wodonga
country: Australia
facility: Border Medical Oncology
city: Graz
country: Austria
facility: MUG-Universitätsklinik für Frauenheilkunde Graz
city: Innsbruck
country: Austria
facility: MUI-Universität für Frauenheilkunde
city: Linz
country: Austria
facility: AKH Linz
city: Linz
country: Austria
facility: BHS Linz
city: Salzburg
country: Austria
facility: SALK-LKH Salzburg, Universitätsklinik für Frauenheilkunde und Geburtshilfe
city: Wien
country: Austria
facility: MUW-AKH Wien
city: Leuven
country: Belgium
facility: UZ Leuven
city: Angers
country: France
facility: ICO Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Caen
country: France
facility: Centre Francois Baclesse
city: Chalon-Sur-Saone
country: France
facility: Centre Hospitalier William Morey
city: Cholet
country: France
facility: Centre Hospitalier de Cholet
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Draguignan
country: France
facility: Centre Hospitalier la Dracénie
city: Gap
country: France
facility: Centre Hospitalier Général de Gap
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble
city: Grenoble
country: France
facility: Hôpital Michallon, Centre Hospitalier Universitaire de Grenoble
city: La Roche sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Levallois-Perret
country: France
facility: Institut d'Oncologie Hartmann
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Hôpital Privé Clairval
city: Marseille
country: France
facility: Institute Paoli Clamettes
city: Metz
country: France
facility: Hôpital Mercy
city: Mont de Marsan
country: France
facility: Hôpital de Mont-de-Marsan
city: Montpellier
country: France
facility: ICM Val d'Aurelle
city: Mulhouse
country: France
facility: Hôpital Emile Muller
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Orleans
country: France
facility: Centre Hospitalier Régional d'Orleans
city: Paris
country: France
facility: Group Hospitalier Saint-Joseph
city: Perpignan
country: France
facility: Centre Catalan d'Oncologie
city: Périgueux
country: France
facility: Clinique Francheville
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Romans-sur-Isère
country: France
facility: HôpitauxDrôme Nord - Site de Ramons
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: Saint Herblain
country: France
facility: ICO Centre René Gauducheau
city: Saint Nazaire
country: France
facility: Clinique Mutualiste de l'Estuaire, Cité Sanitaire
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Thonon-les-Bains
country: France
facility: Centre Hospitalier de Thonon-les-Bains
city: Toulouse
country: France
facility: Clinique Pasteur
city: Toulouse
country: France
facility: Clinique Saint Jean du Languedoc
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique
city: Villeneuve d'Ascq
country: France
facility: Hôpital Privé Villeneuve d'Ascq, Institut de Canérologie
city: Altötting
country: Germany
facility: Kreisklinik Altötting-Burghausen
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Aschaffenburg
country: Germany
facility: Klinikum Aschaffenburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Homburg
country: Germany
facility: Hochtaunus-Klinik
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Berlin
country: Germany
facility: Praxisklinik Krebsheilkunde für Frauen
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt Bochum
city: Bonn
country: Germany
facility: Johanniter-Krankenhaus
city: Bonn
country: Germany
facility: Medizinisches Zentrum Bonn-Friedensplatz
city: Bottrop
country: Germany
facility: Schwerpunktpraxis für Onkologie / Hämatologie
city: Brandenburg
country: Germany
facility: Städtisches Klinikum Brandenburg
city: Braunschweig
country: Germany
facility: Gynäkologisch-Onkologische Gemeinschaftspraxis
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie-Krankenhaus
city: Bremen
country: Germany
facility: Gynaekologicum Bremen
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Deggendorf
country: Germany
facility: Donau-Isar-Kliniken, Klinikum Deggendorf
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dortmund
country: Germany
facility: Klinikum Dortmund
city: Dresden
country: Germany
facility: Onkozentrum Dresden
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Düsseldorf
country: Germany
facility: Evangelisches Krankenhaus Düsseldorf
city: Düsseldorf
country: Germany
facility: Kaiserswerther Diakonie, Florence-Nightingale-Krankenhaus
city: Düsseldorf
country: Germany
facility: Universitätsfrauenklinik Düsseldorf
city: Eggenfelden
country: Germany
facility: Rottal-Inn-Klinik Eggenfelden
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Klinikum Essen Mitte
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Flensburg
country: Germany
facility: DIAKO Flensburg
city: Frankfurt
country: Germany
facility: Agaplesion Markus Krankenhaus
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsfrauenklinik Freiburg
city: Freudenstadt
country: Germany
facility: Kreiskrankenhaus Freudenstadt
city: Fürth
country: Germany
facility: Klinikum Fürth
city: Georgsmarienhütte
country: Germany
facility: Franziskus-Hospital Harderberg
city: Gifhorn
country: Germany
facility: HELIOS-Klinikum Gifhorn
city: Goslar
country: Germany
facility: Onkologische Kooperation Harz
city: Grafing
country: Germany
facility: Die Frauenarztpraxis in Grafing
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Albertinen Krankenhaus
city: Hamburg
country: Germany
facility: Marienkrankenhaus Hamburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hameln
country: Germany
facility: Sana-Klinikum Hameln-Pyrmont
city: Hanau
country: Germany
facility: Klinikum Hanau
city: Hannover
country: Germany
facility: Friederikenstift
city: Hannover
country: Germany
facility: Gynäkologisch-Onkologische Praxis Hannover
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Henstedt-Ulzburg
country: Germany
facility: Paracelsus-Klinik
city: Hildesheim
country: Germany
facility: Praxis Dres. Uleer / Pourfard
city: Itzehoe
country: Germany
facility: Klinikum Itzehoe
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Kempten
country: Germany
facility: Klinikum Kempten
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Kiel
country: Germany
facility: Zentrum für Gynäkologische Onkologie
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Kulmbach
country: Germany
facility: Klinikum Kulmbach
city: Köln
country: Germany
facility: St. Elisabeth-Krankenhaus Hohenlind
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Lich
country: Germany
facility: Asklepios Klinik Lich
city: Limburg
country: Germany
facility: St. Vincenz Krankenhaus
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Lüneburg
country: Germany
facility: Onkologische Schwerpunktpraxis Lüneburg
city: Magdeburg
country: Germany
facility: Klinik St. Marienstift
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Universitätsfrauenklinik Mannheim
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: München
country: Germany
facility: Klinikum rechts der Isar
city: München
country: Germany
facility: LMU München, Frauenklinik Großhadern
city: München
country: Germany
facility: Rotkreuzklinikum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Neumarkt
country: Germany
facility: Kliniken des Landkreises Neumarkt
city: Neuss
country: Germany
facility: Lukaskrankenhaus
city: Nordhausen
country: Germany
facility: MVZ Nordhausen
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Offenbach
country: Germany
facility: Klinikum Offenbach
city: Offenburg
country: Germany
facility: Ortenau-Klinikum
city: Osnabrück
country: Germany
facility: Marienhospital
city: Paderborn
country: Germany
facility: St. Vincenz Krankenhaus
city: Pinneberg
country: Germany
facility: Onkologische Praxis Pinneberg
city: Quedlinburg
country: Germany
facility: Harzklinikum Quedlinburg
city: Ravensburg
country: Germany
facility: Onkologie Ravensburg
city: Rendsburg
country: Germany
facility: imland Klinik Rendsburg
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg
city: Rostock
country: Germany
facility: Universitätsfrauenklinik Rostock
city: Saalfeld
country: Germany
facility: Thüringen-Kliniken
city: Saarbrücken
country: Germany
facility: Caritasklinikum St. Theresia
city: Salzgitter
country: Germany
facility: Praxis Dr. med. W. Dietz
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus
city: Schwerin
country: Germany
facility: HELIOS Kliniken Schwerin
city: Schwäbisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall
city: Siegen
country: Germany
facility: Diakonie Klinikum Jung-Stilling
city: Stadthagen
country: Germany
facility: Klinikum Schaumburg, Krankenhaus Stadthagen
city: Starnberg
country: Germany
facility: Klinikum Starnberg
city: Stralsund
country: Germany
facility: g.Sund Gyn. Kompetenzzentrum
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Suhl
country: Germany
facility: SRH Zentralklinikum Suhl
city: Torgau
country: Germany
facility: Kreiskrankenhaus "J. Kentmann"
city: Traunstein
country: Germany
facility: Klinikum Traunstein
city: Trier
country: Germany
facility: Klinikum Mutterhaus
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
city: Viersen
country: Germany
facility: Praxis Dr. med. W. W. Reiter
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum Villingen-Schwenningen
city: Wetzlar
country: Germany
facility: Lahn-Dill-Kliniken Wetzlar
city: Wiesbaden
country: Germany
facility: Dr. Horst Schmidt Kliniken
city: Wiesbaden
country: Germany
facility: St. Josefs Hospital Wiesbaden
city: Wolfsburg
country: Germany
facility: amO am Klieversberg
city: Worms
country: Germany
facility: Klinikum Worms
city: Zwickau
country: Germany
facility: Heinrich-Braun-Klinikum
city: Bangor
country: United Kingdom
facility: Gwynedd Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Center
city: Rhyl
country: United Kingdom
facility: Glan Clywd Hospital
Study officials:
affiliation: AGO Study Group
name: Jacobus Pfisterer, PhD MD
role: STUDY_CHAIR
References:
citation: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marme F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. doi: 10.1016/S1470-2045(20)30142-X. Epub 2020 Apr 16.