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

Sponsor

AGO Research GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01837251

Collaborator

Arbeitsgemeinschaft Gynaekologische Onkologie Austria (Other), ARCAGY/ GINECO GROUP (Other), Australia New Zealand Gynaecological Oncology Group (Other), Scottish Gynaecological Cancer Study Group (Other)

682

Enrollment

193

Locations

Arms

92.1

Actual Duration (Months)

3.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Platinum-sensitive Ovarian Cancer	Drug: Carboplatin Drug: PLD Biological: Bevacizumab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

682 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 1, 2013

Actual Primary Completion Date :

Jan 1, 2021

Actual Study Completion Date :

Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Arm Patients receive bevacizumab 15 mg/kg iv on day 1 followed by gemcitabine 1000mg/m² iv on day 1 & 8 and carboplatin AUC4 iv on day 1 every 3 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.
Experimental: Research Arm 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.	Drug: Carboplatin Drug: PLD Biological: Bevacizumab

Arm

Intervention/Treatment

No Intervention: Control Arm

Patients receive bevacizumab 15 mg/kg iv on day 1 followed by gemcitabine 1000mg/m² iv on day 1 & 8 and carboplatin AUC4 iv on day 1 every 3 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.

Experimental: Research Arm

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.

Drug: Carboplatin

Drug: PLD

Biological: Bevacizumab

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

biological progression-free survival by serum CA 125 [every 3 weeks until progression or up to 30 months (whichever occurs first)]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma
First disease recurrence >6 months after first-line platinum-based chemotherapy
Patients with measurable or non-measurable disease (RECIST v1.1) or CA 125 assessable disease (GCIG criteria) or histological proven diagnosis of relapse
In case of cytoreductive surgery for recurrence, patients must be able to commence cytotoxic chemo-therapy within 8 weeks after cytoreductive surgery
ECOG PS 0-2
Absolute Neutrophil Count >= 1.5 x 10^{9/L; Platelets >= 100 x 10}9/L; Hemoglobin >= 9.5 g/dL
Patients not receiving anticoagulant medication who have an International Normalized Ratio <= 1.5 and an Activated ProThrombin Time <= 1.5 x ULN
Serum bilirubin <= 2 x ULN; Serum transaminases <= 2.5 x ULN (<= 5 x ULN in the presence of liver metastasis)
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
Normal blood pressure or adequately treated and controlled hypertension (either systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg)

Exclusion Criteria:

Ovarian tumors of low malignant potential
Malignancies other than ovarian cancer within 5 years prior to randomization
Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period
Any previous radiotherapy to the abdomen or pelvis
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
Current or recent chronic use of aspirin > 325 mg/day
Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of Bevacizumab
History of VEGF therapy related abdominal fistula or gastrointestinal perforation
Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease
Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
Previous Cerebro-Vascular Accident , Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage
Prior history of hypertensive crisis or hypertensive encephalopathy
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
LVEF defined by ECHO/MUGA below the institutional lower limit of normal
Significant traumatic injury during 4 weeks prior to randomization
Current brain metastases or spinal cord compression
History or evidence upon neurological examination of central nervous system disease
Non-healing wound, active ulcer or bone fracture
History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic coagulation)
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
Pregnant or lactating women
Requirement of therapeutic anticoagulation using marcumar, warfarin or PTT-prolonging heparin

Contacts and Locations

Locations

	Site	City	Country
1	Bankstown-Lidcombe Hospital	Bankstown	Australia
2	Chris O'Brien Lifehouse	Camperdown	Australia
3	NCCI - Coffs Harbour Hospital	Coffs Harbour	Australia
4	The Townsville Hospital	Douglas	Australia
5	Peninsula Health - Frankston Hospital	Frankston	Australia
6	Andrew Love Cancer Centre Geelong	Geelong	Australia
7	Royal Brisbane & Women's Hospital	Herston	Australia
8	Royal Hobart Hospital	Hobart	Australia
9	St. George Hospital	Kogarah	Australia
10	ICON Cancer Care Centre	Milton	Australia
11	Nambour General Hospital	Nambour	Australia
12	Sir Charles Gairdner	Nedlands	Australia
13	North Coast Cancer Institute	Port Macquarie	Australia
14	Royal Hospital for Women	Randwick	Australia
15	Mater Adult Hospital	South Brisbane	Australia
16	Gold Coast University Hospital	Southport	Australia
17	Royal North Shore Hospital	St. Leonards	Australia
18	St. John of God Hospital	Subiaco	Australia
19	Border Medical Oncology	Wodonga	Australia
20	MUG-Universitätsklinik für Frauenheilkunde Graz	Graz	Austria
21	MUI-Universität für Frauenheilkunde	Innsbruck	Austria
22	AKH Linz	Linz	Austria
23	BHS Linz	Linz	Austria
24	SALK-LKH Salzburg, Universitätsklinik für Frauenheilkunde und Geburtshilfe	Salzburg	Austria
25	MUW-AKH Wien	Wien	Austria
26	UZ Leuven	Leuven	Belgium
27	ICO Paul Papin	Angers	France
28	Institut Sainte Catherine	Avignon	France
29	Centre Hospitalier de Blois	Blois	France
30	Clinique Tivoli	Bordeaux	France
31	Polyclinique Bordeaux Nord	Bordeaux	France
32	Centre Francois Baclesse	Caen	France
33	Centre Hospitalier William Morey	Chalon-Sur-Saone	France
34	Centre Hospitalier de Cholet	Cholet	France
35	Hôpital Antoine Béclère	Clamart	France
36	Centre Jean Perrin	Clermont-Ferrand	France
37	Centre Hospitalier la Dracénie	Draguignan	France
38	Centre Hospitalier Général de Gap	Gap	France
39	Groupe Hospitalier Mutualiste de Grenoble	Grenoble	France
40	Hôpital Michallon, Centre Hospitalier Universitaire de Grenoble	Grenoble	France
41	Centre Hospitalier Départemental Les Oudairies	La Roche sur Yon	France
42	Institut d'Oncologie Hartmann	Levallois-Perret	France
43	Centre Oscar Lambret	Lille	France
44	Hôpital Privé Clairval	Marseille	France
45	Institute Paoli Clamettes	Marseille	France
46	Hôpital Mercy	Metz	France
47	Hôpital de Mont-de-Marsan	Mont de Marsan	France
48	ICM Val d'Aurelle	Montpellier	France
49	Hôpital Emile Muller	Mulhouse	France
50	Centre d'Oncologie de Gentilly	Nancy	France
51	Centre Catherine de Sienne	Nantes	France
52	Centre Hospitalier Régional d'Orleans	Orleans	France
53	Group Hospitalier Saint-Joseph	Paris	France
54	Centre Catalan d'Oncologie	Perpignan	France
55	Clinique Francheville	Périgueux	France
56	Centre Eugène Marquis	Rennes	France
57	HôpitauxDrôme Nord - Site de Ramons	Romans-sur-Isère	France
58	Centre Henri Becquerel	Rouen	France
59	Clinique Armoricaine de Radiologie	Saint Brieuc	France
60	ICO Centre René Gauducheau	Saint Herblain	France
61	Clinique Mutualiste de l'Estuaire, Cité Sanitaire	Saint Nazaire	France
62	Centre Paul Strauss	Strasbourg	France
63	Hôpitaux Universitaires de Strasbourg	Strasbourg	France
64	Centre Hospitalier de Thonon-les-Bains	Thonon-les-Bains	France
65	Clinique Pasteur	Toulouse	France
66	Clinique Saint Jean du Languedoc	Toulouse	France
67	Centre Hospitalier Bretagne Atlantique	Vannes	France
68	Hôpital Privé Villeneuve d'Ascq, Institut de Canérologie	Villeneuve d'Ascq	France
69	Kreisklinik Altötting-Burghausen	Altötting	Germany
70	Klinikum St. Marien	Amberg	Germany
71	Klinikum Aschaffenburg	Aschaffenburg	Germany
72	Klinikum Augsburg	Augsburg	Germany
73	Hochtaunus-Klinik	Bad Homburg	Germany
74	Charité - Universitätsmedizin Berlin	Berlin	Germany
75	HELIOS Klinikum Berlin-Buch	Berlin	Germany
76	Praxisklinik Krebsheilkunde für Frauen	Berlin	Germany
77	Augusta-Kranken-Anstalt Bochum	Bochum	Germany
78	Johanniter-Krankenhaus	Bonn	Germany
79	Medizinisches Zentrum Bonn-Friedensplatz	Bonn	Germany
80	Schwerpunktpraxis für Onkologie / Hämatologie	Bottrop	Germany
81	Städtisches Klinikum Brandenburg	Brandenburg	Germany
82	Gynäkologisch-Onkologische Gemeinschaftspraxis	Braunschweig	Germany
83	DIAKO Ev. Diakonie-Krankenhaus	Bremen	Germany
84	Gynaekologicum Bremen	Bremen	Germany
85	Klinikum Bremen-Mitte	Bremen	Germany
86	Klinikum Chemnitz	Chemnitz	Germany
87	Klinikum Darmstadt	Darmstadt	Germany
88	Donau-Isar-Kliniken, Klinikum Deggendorf	Deggendorf	Germany
89	Städtisches Klinikum Dessau	Dessau	Germany
90	Klinikum Dortmund	Dortmund	Germany
91	Onkozentrum Dresden	Dresden	Germany
92	Universitätsklinikum Carl Gustav Carus	Dresden	Germany
93	Evangelisches Krankenhaus Düsseldorf	Düsseldorf	Germany
94	Kaiserswerther Diakonie, Florence-Nightingale-Krankenhaus	Düsseldorf	Germany
95	Universitätsfrauenklinik Düsseldorf	Düsseldorf	Germany
96	Rottal-Inn-Klinik Eggenfelden	Eggenfelden	Germany
97	Universitätsklinikum Erlangen	Erlangen	Germany
98	Klinikum Essen Mitte	Essen	Germany
99	Universitätsklinikum Essen	Essen	Germany
100	Klinikum Esslingen	Esslingen	Germany
101	DIAKO Flensburg	Flensburg	Germany
102	Agaplesion Markus Krankenhaus	Frankfurt	Germany
103	Klinikum Frankfurt Höchst	Frankfurt	Germany
104	Universitätsklinikum Frankfurt	Frankfurt	Germany
105	Universitätsfrauenklinik Freiburg	Freiburg	Germany
106	Kreiskrankenhaus Freudenstadt	Freudenstadt	Germany
107	Klinikum Fürth	Fürth	Germany
108	Franziskus-Hospital Harderberg	Georgsmarienhütte	Germany
109	HELIOS-Klinikum Gifhorn	Gifhorn	Germany
110	Onkologische Kooperation Harz	Goslar	Germany
111	Die Frauenarztpraxis in Grafing	Grafing	Germany
112	Universitätsmedizin Greifswald	Greifswald	Germany
113	Universitätsklinikum Halle	Halle	Germany
114	Albertinen Krankenhaus	Hamburg	Germany
115	Marienkrankenhaus Hamburg	Hamburg	Germany
116	Universitätsklinikum Hamburg-Eppendorf	Hamburg	Germany
117	Sana-Klinikum Hameln-Pyrmont	Hameln	Germany
118	Klinikum Hanau	Hanau	Germany
119	Friederikenstift	Hannover	Germany
120	Gynäkologisch-Onkologische Praxis Hannover	Hannover	Germany
121	Medizinische Hochschule Hannover	Hannover	Germany
122	Universitätsklinikum Heidelberg	Heidelberg	Germany
123	Paracelsus-Klinik	Henstedt-Ulzburg	Germany
124	Praxis Dres. Uleer / Pourfard	Hildesheim	Germany
125	Klinikum Itzehoe	Itzehoe	Germany
126	Universitätsklinikum Jena	Jena	Germany
127	St. Vincentius Kliniken	Karlsruhe	Germany
128	Klinikum Kassel	Kassel	Germany
129	Klinikum Kempten	Kempten	Germany
130	Universitätsklinikum Schleswig-Holstein	Kiel	Germany
131	Zentrum für Gynäkologische Onkologie	Kiel	Germany
132	Klinikum Konstanz	Konstanz	Germany
133	Klinikum Kulmbach	Kulmbach	Germany
134	St. Elisabeth-Krankenhaus Hohenlind	Köln	Germany
135	Universitätsklinikum Köln	Köln	Germany
136	Asklepios Klinik Lich	Lich	Germany
137	St. Vincenz Krankenhaus	Limburg	Germany
138	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck	Germany
139	Onkologische Schwerpunktpraxis Lüneburg	Lüneburg	Germany
140	Klinik St. Marienstift	Magdeburg	Germany
141	Universitätsklinikum Magdeburg	Magdeburg	Germany
142	Universitätsmedizin Mainz	Mainz	Germany
143	Universitätsfrauenklinik Mannheim	Mannheim	Germany
144	Universitätsklinikum Gießen und Marburg	Marburg	Germany
145	Johannes Wesling Klinikum	Minden	Germany
146	Klinikum rechts der Isar	München	Germany
147	LMU München, Frauenklinik Großhadern	München	Germany
148	Rotkreuzklinikum München	München	Germany
149	Universitätsklinikum Münster	Münster	Germany
150	Kliniken des Landkreises Neumarkt	Neumarkt	Germany
151	Lukaskrankenhaus	Neuss	Germany
152	MVZ Nordhausen	Nordhausen	Germany
153	Klinikum Nürnberg	Nürnberg	Germany
154	Klinikum Offenbach	Offenbach	Germany
155	Ortenau-Klinikum	Offenburg	Germany
156	Marienhospital	Osnabrück	Germany
157	St. Vincenz Krankenhaus	Paderborn	Germany
158	Onkologische Praxis Pinneberg	Pinneberg	Germany
159	Harzklinikum Quedlinburg	Quedlinburg	Germany
160	Onkologie Ravensburg	Ravensburg	Germany
161	imland Klinik Rendsburg	Rendsburg	Germany
162	Klinikum am Steinenberg	Reutlingen	Germany
163	Universitätsfrauenklinik Rostock	Rostock	Germany
164	Thüringen-Kliniken	Saalfeld	Germany
165	Caritasklinikum St. Theresia	Saarbrücken	Germany
166	Praxis Dr. med. W. Dietz	Salzgitter	Germany
167	Leopoldina-Krankenhaus	Schweinfurt	Germany
168	HELIOS Kliniken Schwerin	Schwerin	Germany
169	Diakonie-Klinikum Schwäbisch Hall	Schwäbisch Hall	Germany
170	Diakonie Klinikum Jung-Stilling	Siegen	Germany
171	Klinikum Schaumburg, Krankenhaus Stadthagen	Stadthagen	Germany
172	Klinikum Starnberg	Starnberg	Germany
173	g.Sund Gyn. Kompetenzzentrum	Stralsund	Germany
174	Marienhospital Stuttgart	Stuttgart	Germany
175	Robert-Bosch-Krankenhaus	Stuttgart	Germany
176	SRH Zentralklinikum Suhl	Suhl	Germany
177	Kreiskrankenhaus "J. Kentmann"	Torgau	Germany
178	Klinikum Traunstein	Traunstein	Germany
179	Klinikum Mutterhaus	Trier	Germany
180	Universitätsklinikum Tübingen	Tübingen	Germany
181	Universitätsfrauenklinik Ulm	Ulm	Germany
182	Praxis Dr. med. W. W. Reiter	Viersen	Germany
183	Schwarzwald-Baar Klinikum Villingen-Schwenningen	Villingen-Schwenningen	Germany
184	Lahn-Dill-Kliniken Wetzlar	Wetzlar	Germany
185	Dr. Horst Schmidt Kliniken	Wiesbaden	Germany
186	St. Josefs Hospital Wiesbaden	Wiesbaden	Germany
187	amO am Klieversberg	Wolfsburg	Germany
188	Klinikum Worms	Worms	Germany
189	Heinrich-Braun-Klinikum	Zwickau	Germany
190	Gwynedd Hospital	Bangor	United Kingdom
191	Velindre Cancer Centre	Cardiff	United Kingdom
192	The Beatson West of Scotland Cancer Center	Glasgow	United Kingdom
193	Glan Clywd Hospital	Rhyl	United Kingdom