Evaluation of Optimal Treatment With Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Phase 3

Completed

• Conditions: Recurrent Platinum-sensitive Ovarian Cancer
• Interventions: Drug: Carboplatin; Drug: PLD; Biological: Bevacizumab

• Registration Number: NCT01837251
• Lead Sponsor: AGO Research GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-16
• Study First Submitted QC: 2013-04-22
• Study First Posted: 2013-04-23
• Study Start: 2013-05
• Primary Completion: 2021-01
• Study Completion: 2021-01
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-08
• Last Update Posted: 2021-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 682

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Research Arm	PLD	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.
Research Arm	Bevacizumab	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.
Research Arm	Carboplatin	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.

Primary Outcome Measures

Name	Time	Method
investigator-determined progression-free survival	every 12 weeks until progression or up to 30 months (whichever occurs first)

Secondary Outcome Measures

Name	Time	Method
Health related Quality of Life (QoL)	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)
Safety and Tolerability, i.e. type, frequency, severity and duration o adverse reactions	every 3 weeks, 30 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later)
Overall Survival	every 3 weeks during treatment with bevacizumab, thereafter every 6 months; for up 30 months
biological progression-free survival by serum CA 125	every 3 weeks until progression or up to 30 months (whichever occurs first)

Trial Locations

Locations (192)

ICON Cancer Care Centre; 🇦🇺 Milton, Australia

St. George Hospital; 🇦🇺 Kogarah, Australia

Mater Adult Hospital; 🇦🇺 South Brisbane, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

Hôpital Michallon, Centre Hospitalier Universitaire de Grenoble; 🇫🇷 Grenoble, France

Centre Catalan d'Oncologie; 🇫🇷 Perpignan, France

UZ Leuven; 🇧🇪 Leuven, Belgium

Centre Francois Baclesse; 🇫🇷 Caen, France

Hôpital de Mont-de-Marsan; 🇫🇷 Mont de Marsan, France

ICO Paul Papin; 🇫🇷 Angers, France

Centre Hospitalier de Blois; 🇫🇷 Blois, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Centre Hospitalier la Dracénie; 🇫🇷 Draguignan, France

Peninsula Health - Frankston Hospital; 🇦🇺 Frankston, Australia

Andrew Love Cancer Centre Geelong; 🇦🇺 Geelong, Australia

Royal North Shore Hospital; 🇦🇺 St. Leonards, Australia

Centre Hospitalier Général de Gap; 🇫🇷 Gap, France

Hôpital Privé Clairval; 🇫🇷 Marseille, France

Centre Hospitalier William Morey; 🇫🇷 Chalon-Sur-Saone, France

Royal Hospital for Women; 🇦🇺 Randwick, Australia

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

NCCI - Coffs Harbour Hospital; 🇦🇺 Coffs Harbour, Australia

Sir Charles Gairdner; 🇦🇺 Nedlands, Australia

North Coast Cancer Institute; 🇦🇺 Port Macquarie, Australia

Centre Hospitalier Départemental Les Oudairies; 🇫🇷 La Roche sur Yon, France

Klinikum Essen Mitte; 🇩🇪 Essen, Germany

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Franziskus-Hospital Harderberg; 🇩🇪 Georgsmarienhütte, Germany

Evangelisches Krankenhaus Düsseldorf; 🇩🇪 Düsseldorf, Germany

Clinique Tivoli; 🇫🇷 Bordeaux, France

Universitätsfrauenklinik Düsseldorf; 🇩🇪 Düsseldorf, Germany

Institute Paoli Clamettes; 🇫🇷 Marseille, France

Klinikum Bremen-Mitte; 🇩🇪 Bremen, Germany

Hôpital Antoine Béclère; 🇫🇷 Clamart, France

Groupe Hospitalier Mutualiste de Grenoble; 🇫🇷 Grenoble, France

Centre d'Oncologie de Gentilly; 🇫🇷 Nancy, France

Praxisklinik Krebsheilkunde für Frauen; 🇩🇪 Berlin, Germany

DIAKO Ev. Diakonie-Krankenhaus; 🇩🇪 Bremen, Germany

Gynaekologicum Bremen; 🇩🇪 Bremen, Germany

Centre Hospitalier de Thonon-les-Bains; 🇫🇷 Thonon-les-Bains, France

Schwerpunktpraxis für Onkologie / Hämatologie; 🇩🇪 Bottrop, Germany

Klinikum Darmstadt; 🇩🇪 Darmstadt, Germany

Onkozentrum Dresden; 🇩🇪 Dresden, Germany

Städtisches Klinikum Brandenburg; 🇩🇪 Brandenburg, Germany

Städtisches Klinikum Dessau; 🇩🇪 Dessau, Germany

Gynäkologisch-Onkologische Gemeinschaftspraxis; 🇩🇪 Braunschweig, Germany

Rottal-Inn-Klinik Eggenfelden; 🇩🇪 Eggenfelden, Germany

Hochtaunus-Klinik; 🇩🇪 Bad Homburg, Germany

Klinikum Chemnitz; 🇩🇪 Chemnitz, Germany

Klinikum Aschaffenburg; 🇩🇪 Aschaffenburg, Germany

Klinikum St. Marien; 🇩🇪 Amberg, Germany

Klinikum Itzehoe; 🇩🇪 Itzehoe, Germany

Kreiskrankenhaus "J. Kentmann"; 🇩🇪 Torgau, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Glan Clywd Hospital; 🇬🇧 Rhyl, United Kingdom

Universitätsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Klinikum Hanau; 🇩🇪 Hanau, Germany

Diakonie Klinikum Jung-Stilling; 🇩🇪 Siegen, Germany

Praxis Dr. med. W. W. Reiter; 🇩🇪 Viersen, Germany

Praxis Dr. med. W. Dietz; 🇩🇪 Salzgitter, Germany

HELIOS Kliniken Schwerin; 🇩🇪 Schwerin, Germany

Klinikum Schaumburg, Krankenhaus Stadthagen; 🇩🇪 Stadthagen, Germany

Dr. Horst Schmidt Kliniken; 🇩🇪 Wiesbaden, Germany

Velindre Cancer Centre; 🇬🇧 Cardiff, United Kingdom

Lahn-Dill-Kliniken Wetzlar; 🇩🇪 Wetzlar, Germany

MUI-Universität für Frauenheilkunde; 🇦🇹 Innsbruck, Austria

BHS Linz; 🇦🇹 Linz, Austria

SALK-LKH Salzburg, Universitätsklinik für Frauenheilkunde und Geburtshilfe; 🇦🇹 Salzburg, Austria

MUG-Universitätsklinik für Frauenheilkunde Graz; 🇦🇹 Graz, Austria

MUW-AKH Wien; 🇦🇹 Wien, Austria

The Beatson West of Scotland Cancer Center; 🇬🇧 Glasgow, United Kingdom

Centre Hospitalier de Cholet; 🇫🇷 Cholet, France

Institut d'Oncologie Hartmann; 🇫🇷 Levallois-Perret, France

ICM Val d'Aurelle; 🇫🇷 Montpellier, France

Group Hospitalier Saint-Joseph; 🇫🇷 Paris, France

Centre Hospitalier Régional d'Orleans; 🇫🇷 Orleans, France

Centre Catherine de Sienne; 🇫🇷 Nantes, France

Clinique Francheville; 🇫🇷 Périgueux, France

Clinique Mutualiste de l'Estuaire, Cité Sanitaire; 🇫🇷 Saint Nazaire, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France

Clinique Pasteur; 🇫🇷 Toulouse, France

Augusta-Kranken-Anstalt Bochum; 🇩🇪 Bochum, Germany

Medizinisches Zentrum Bonn-Friedensplatz; 🇩🇪 Bonn, Germany

Donau-Isar-Kliniken, Klinikum Deggendorf; 🇩🇪 Deggendorf, Germany

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Klinikum Dortmund; 🇩🇪 Dortmund, Germany

Klinikum Esslingen; 🇩🇪 Esslingen, Germany

DIAKO Flensburg; 🇩🇪 Flensburg, Germany

Albertinen Krankenhaus; 🇩🇪 Hamburg, Germany

Universitätsmedizin Greifswald; 🇩🇪 Greifswald, Germany

Klinikum Frankfurt Höchst; 🇩🇪 Frankfurt, Germany

Universitätsfrauenklinik Freiburg; 🇩🇪 Freiburg, Germany

Kreiskrankenhaus Freudenstadt; 🇩🇪 Freudenstadt, Germany

Universitätsklinikum Halle; 🇩🇪 Halle, Germany

HELIOS-Klinikum Gifhorn; 🇩🇪 Gifhorn, Germany

Marienkrankenhaus Hamburg; 🇩🇪 Hamburg, Germany

Sana-Klinikum Hameln-Pyrmont; 🇩🇪 Hameln, Germany

Friederikenstift; 🇩🇪 Hannover, Germany

Gynäkologisch-Onkologische Praxis Hannover; 🇩🇪 Hannover, Germany

Paracelsus-Klinik; 🇩🇪 Henstedt-Ulzburg, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Praxis Dres. Uleer / Pourfard; 🇩🇪 Hildesheim, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

Klinikum Kassel; 🇩🇪 Kassel, Germany

Klinikum Kempten; 🇩🇪 Kempten, Germany

St. Vincentius Kliniken; 🇩🇪 Karlsruhe, Germany

Zentrum für Gynäkologische Onkologie; 🇩🇪 Kiel, Germany

Klinikum Konstanz; 🇩🇪 Konstanz, Germany

Onkologische Schwerpunktpraxis Lüneburg; 🇩🇪 Lüneburg, Germany

St. Elisabeth-Krankenhaus Hohenlind; 🇩🇪 Köln, Germany

Universitätsklinikum Köln; 🇩🇪 Köln, Germany

Klinik St. Marienstift; 🇩🇪 Magdeburg, Germany

LMU München, Frauenklinik Großhadern; 🇩🇪 München, Germany

Rotkreuzklinikum München; 🇩🇪 München, Germany

Universitätsklinikum Gießen und Marburg; 🇩🇪 Marburg, Germany

Universitätsmedizin Mainz; 🇩🇪 Mainz, Germany

Johannes Wesling Klinikum; 🇩🇪 Minden, Germany

Kliniken des Landkreises Neumarkt; 🇩🇪 Neumarkt, Germany

MVZ Nordhausen; 🇩🇪 Nordhausen, Germany

Klinikum Offenbach; 🇩🇪 Offenbach, Germany

Marienhospital; 🇩🇪 Osnabrück, Germany

Onkologische Praxis Pinneberg; 🇩🇪 Pinneberg, Germany

Harzklinikum Quedlinburg; 🇩🇪 Quedlinburg, Germany

imland Klinik Rendsburg; 🇩🇪 Rendsburg, Germany

Onkologie Ravensburg; 🇩🇪 Ravensburg, Germany

Klinikum am Steinenberg; 🇩🇪 Reutlingen, Germany

Universitätsfrauenklinik Rostock; 🇩🇪 Rostock, Germany

Thüringen-Kliniken; 🇩🇪 Saalfeld, Germany

Caritasklinikum St. Theresia; 🇩🇪 Saarbrücken, Germany

Marienhospital Stuttgart; 🇩🇪 Stuttgart, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Diakonie-Klinikum Schwäbisch Hall; 🇩🇪 Schwäbisch Hall, Germany

SRH Zentralklinikum Suhl; 🇩🇪 Suhl, Germany

Klinikum Mutterhaus; 🇩🇪 Trier, Germany

Schwarzwald-Baar Klinikum Villingen-Schwenningen; 🇩🇪 Villingen-Schwenningen, Germany

Heinrich-Braun-Klinikum; 🇩🇪 Zwickau, Germany

amO am Klieversberg; 🇩🇪 Wolfsburg, Germany

Gold Coast University Hospital; 🇦🇺 Southport, Australia

St. John of God Hospital; 🇦🇺 Subiaco, Australia

Border Medical Oncology; 🇦🇺 Wodonga, Australia

HELIOS Klinikum Berlin-Buch; 🇩🇪 Berlin, Germany

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, Australia

Bankstown-Lidcombe Hospital; 🇦🇺 Bankstown, Australia

Nambour General Hospital; 🇦🇺 Nambour, Australia

AKH Linz; 🇦🇹 Linz, Austria

Polyclinique Bordeaux Nord; 🇫🇷 Bordeaux, France

Institut Sainte Catherine; 🇫🇷 Avignon, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Hôpital Mercy; 🇫🇷 Metz, France

Hôpital Emile Muller; 🇫🇷 Mulhouse, France

HôpitauxDrôme Nord - Site de Ramons; 🇫🇷 Romans-sur-Isère, France

Centre Eugène Marquis; 🇫🇷 Rennes, France

Clinique Armoricaine de Radiologie; 🇫🇷 Saint Brieuc, France

ICO Centre René Gauducheau; 🇫🇷 Saint Herblain, France

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France

Clinique Saint Jean du Languedoc; 🇫🇷 Toulouse, France

Hôpital Privé Villeneuve d'Ascq, Institut de Canérologie; 🇫🇷 Villeneuve d'Ascq, France

Kreisklinik Altötting-Burghausen; 🇩🇪 Altötting, Germany

Johanniter-Krankenhaus; 🇩🇪 Bonn, Germany

Klinikum Augsburg; 🇩🇪 Augsburg, Germany

Kaiserswerther Diakonie, Florence-Nightingale-Krankenhaus; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

Agaplesion Markus Krankenhaus; 🇩🇪 Frankfurt, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Onkologische Kooperation Harz; 🇩🇪 Goslar, Germany

Die Frauenarztpraxis in Grafing; 🇩🇪 Grafing, Germany

Klinikum Fürth; 🇩🇪 Fürth, Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck; 🇩🇪 Lübeck, Germany

Universitätsklinikum Magdeburg; 🇩🇪 Magdeburg, Germany

Klinikum rechts der Isar; 🇩🇪 München, Germany

Lukaskrankenhaus; 🇩🇪 Neuss, Germany

Universitätsfrauenklinik Mannheim; 🇩🇪 Mannheim, Germany

Klinikum Nürnberg; 🇩🇪 Nürnberg, Germany

Ortenau-Klinikum; 🇩🇪 Offenburg, Germany

Klinikum Starnberg; 🇩🇪 Starnberg, Germany

g.Sund Gyn. Kompetenzzentrum; 🇩🇪 Stralsund, Germany

St. Josefs Hospital Wiesbaden; 🇩🇪 Wiesbaden, Germany

Klinikum Traunstein; 🇩🇪 Traunstein, Germany

Robert-Bosch-Krankenhaus; 🇩🇪 Stuttgart, Germany

Universitätsfrauenklinik Ulm; 🇩🇪 Ulm, Germany

Gwynedd Hospital; 🇬🇧 Bangor, United Kingdom

Centre Hospitalier Bretagne Atlantique; 🇫🇷 Vannes, France

Klinikum Kulmbach; 🇩🇪 Kulmbach, Germany

Asklepios Klinik Lich; 🇩🇪 Lich, Germany

The Townsville Hospital; 🇦🇺 Douglas, Australia

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Royal Brisbane & Women's Hospital; 🇦🇺 Herston, Australia

St. Vincenz Krankenhaus; 🇩🇪 Paderborn, Germany

Klinikum Worms; 🇩🇪 Worms, Germany

Leopoldina-Krankenhaus; 🇩🇪 Schweinfurt, Germany