Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Newly Diagnosed Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

NCT ID: NCT00483782

Last Updated: 2013-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1520 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel together with bevacizumab is more effective than carboplatin and paclitaxel alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

PURPOSE: This randomized phase III trial is studying carboplatin, paclitaxel, and bevacizumab to see how well they work compared with carboplatin and paclitaxel alone in treating patients with newly diagnosed ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed Description

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OBJECTIVES:

Primary

* Compare the progression-free survival and overall survival of patients with newly diagnosed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer treated with carboplatin and paclitaxel with vs without bevacizumab.

Secondary

* Compare the response rate in patients treated with these regimens.
* Compare the duration of tumor response in patients treated with these regimens.
* Compare the biological progression-free interval, as measured by increasing CA 125 levels, in patients treated with these regimens.
* Compare the safety (e.g., adverse events, laboratory results, and performance status) of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.
* Compare the cost-effectiveness of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to FIGO stage (stage I-III with residual disease ≤ 1 cm vs stage I-III with residual disease \> 1 cm vs stage IV disease), intended time to start chemotherapy after surgery (≤ 4 weeks vs \> 4 weeks), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I (control): Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive bevacizumab IV over 30-90 minutes followed by paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab alone every 3 weeks for 12 courses.

Quality of life is assessed at baseline, before every course, every 6 weeks for 1 year, every 3 months until disease progression or for up to 2 years, and then at 3 years. Health economic data is assessed periodically, including days of inpatient hospitalization visits, outpatient visits, and use of anticancer therapies.

After completion of study treatment, patients are followed every 3-6 months for 5 years and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Conditions

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Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer

Keywords

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stage IV ovarian epithelial cancer Brenner tumor ovarian carcinosarcoma ovarian clear cell cystadenocarcinoma ovarian endometrioid adenocarcinoma ovarian mixed epithelial carcinoma ovarian mucinous cystadenocarcinoma ovarian serous cystadenocarcinoma ovarian undifferentiated adenocarcinoma stage IA ovarian epithelial cancer stage IB ovarian epithelial cancer stage IC ovarian epithelial cancer stage IIA ovarian epithelial cancer stage IIB ovarian epithelial cancer stage IIC ovarian epithelial cancer stage IIIA ovarian epithelial cancer stage IIIB ovarian epithelial cancer stage IIIC ovarian epithelial cancer stage IA fallopian tube cancer stage IB fallopian tube cancer stage IC fallopian tube cancer stage IIA fallopian tube cancer stage IIB fallopian tube cancer stage IIC fallopian tube cancer stage IIIA fallopian tube cancer stage IIIB fallopian tube cancer stage IIIC fallopian tube cancer stage IV fallopian tube cancer stage IA primary peritoneal cavity cancer stage IB primary peritoneal cavity cancer stage IC primary peritoneal cavity cancer stage IIA primary peritoneal cavity cancer stage IIB primary peritoneal cavity cancer stage IIC primary peritoneal cavity cancer stage IIIA primary peritoneal cavity cancer stage IIIB primary peritoneal cavity cancer stage IIIC primary peritoneal cavity cancer stage IV primary peritoneal cavity cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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bevacizumab

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

questionnaire administration

Intervention Type OTHER

study of socioeconomic and demographic variables

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Stage IV disease diagnosed by histology
* No planned surgery prior to disease progression, including interval debulking surgery
* Patients with prior early-stage ovarian epithelial or fallopian tube carcinoma treated with surgery alone are eligible at the time of diagnosis of abdominopelvic recurrence provided no further interval cytoreductive therapy is planned prior to disease progression
* Synchronous primary endometrial carcinoma or a past history of primary endometrial carcinoma allowed provided the following criteria are met:

* Disease ≤ stage IB
* No more than superficial myometrial invasion
* No lymphovascular invasion
* Not poorly differentiated (i.e., no grade 3, papillary serous, or clear cell disease)
* Measurable or nonmeasurable disease
* No ovarian nonepithelial cancer, including malignant mixed Müllerian tumors
* No borderline tumors (e.g., tumors of low malignant potential)
* No history or clinical suspicion of brain metastases or spinal cord compression

* CT scan or MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases
* Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 12 weeks
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (can be post-transfusion)
* INR ≤ 1.5
* APTT ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* ALT and AST ≤ 2.5 times ULN
* Creatinine ≤ 2.0 mg/dL
* Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 weeks after completion of study therapy
* No significant traumatic injury within the past 4 weeks
* No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
* No other malignancies within the past 5 years except for adequately treated carcinoma in situ of the cervix, and/or basal cell skin cancer, and/or early endometrial carcinoma
* No pre-existing sensory or motor neuropathy ≥ grade 2
* No history or evidence of CNS disease (e.g., uncontrolled seizures) by neurological examination unless adequately treated with standard medical therapy
* No history or evidence of thrombotic or hemorrhagic disorders
* No uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg despite antihypertensive therapy)
* No known hypersensitivity to bevacizumab and its excipients, chemotherapy, or Cremophor EL
* No nonhealing wound, ulcer, or bone fracture

* Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations
* No clinically significant cardiovascular disease, including any of the following:

* Myocardial infarction or unstable angina within the past 6 months
* New York Heart Association class II-IV congestive heart failure
* Poorly controlled cardiac arrhythmia despite medication

* Rate-controlled atrial fibrillation allowed
* Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with activities of daily living requiring repair or revision)
* No evidence of other disease or condition, metabolic dysfunction, physical examination findings, or laboratory findings that would contraindicate the use of an investigational drug or put the patient at high-risk for treatment-related complications

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 4 weeks since other prior surgery or open biopsy
* No prior systemic therapy for ovarian cancer (e.g., chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy, or hormonal therapy)
* Prior adjuvant chemotherapy allowed for other malignancies (e.g., breast or colorectal carcinoma) if malignancy was diagnosed over 5 years ago with no evidence of subsequent recurrence
* No prior mouse CA 125 antibody
* No prior radiotherapy to the abdomen or pelvis
* More than 10 days since prior and no concurrent chronic use of acetylsalicylic acid (\> 325 mg/day)

* Low-dose (\< 325 mg/day) acetylsalicylic acid allowed
* More than 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes

* Use of therapy for line patency allowed provided INR \< 1.5
* More than 30 days since prior and no other concurrent investigational agent or participation in another clinical trial
* No other concurrent systemic antitumor agents
* No concurrent surgery
* No concurrent maintenance chemotherapy or intraperitoneal chemotherapy (including cytotoxic chemotherapy)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Council

OTHER_GOV

Sponsor Role lead

Principal Investigators

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Tim J. Perren, MD

Role: STUDY_CHAIR

Leeds Cancer Centre at St. James's University Hospital

Locations

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Cancer Therapy Centre at Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Prince of Wales Private Hospital

Randwick, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Sydney Cancer Centre at Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Site Status

Newcastle Mater Misericordiae Hospital

Waratah, New South Wales, Australia

Site Status

Westmead Institute for Cancer Research at Westmead Hospital

Wentworthville, New South Wales, Australia

Site Status

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Site Status

Mater Adult Hospital

South Brisbane, Queensland, Australia

Site Status

Royal Adelaide Hospital Cancer Centre

Adelaide, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Royal Women's Hospital

Carlton, Victoria, Australia

Site Status

Mercy Hospital for Women

East Melbourne, Victoria, Australia

Site Status

Frankston Hospital

Frankston, Victoria, Australia

Site Status

Murray Valley Private Hospital and Cancer Treatment Centre

Wodonga, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital - Perth

Perth, Western Australia, Australia

Site Status

Centre Paul Papin

Angers, , France

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Institut Sainte Catherine

Avignon, , France

Site Status

Institut Bergonie

Bordeaux, , France

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Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

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Clinique Tivoli

Bordeaux, , France

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Centre Regional Francois Baclesse

Caen, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

Hopital Louis Pasteur

Colmar, , France

Site Status

CHU de Grenoble - Hopital de la Tronche

Grenoble, , France

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Institut Prive de Cancerologie

Grenoble, , France

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Hopital Andre Mignot

Le Chesnay, , France

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Centre Jean Bernard

Le Mans, , France

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Centre Leon Berard

Lyon, , France

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Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Site Status

Centre D'Oncologie De Gentilly

Nancy, , France

Site Status

Centre Catherine de Sienne

Nantes, , France

Site Status

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

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Institut Curie Hopital

Paris, , France

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Hotel Dieu de Paris

Paris, , France

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Hopital Cochin

Paris, , France

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Hopital Tenon

Paris, , France

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Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

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Centre Henri Becquerel

Rouen, , France

Site Status

Clinique Armoricaine De Radiologie

Saint-Brieuc, , France

Site Status

Centre Rene Huguenin

Saint-Cloud, , France

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Hopital Universitaire Hautepierre

Strasbourg, , France

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Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

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Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

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Evang. Waldkrankenhaus Spandau

Berlin, , Germany

Site Status

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

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Klinikum Bremen-Mitte

Bremen, , Germany

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Praxis Dres. F.& G. Doering

Bremen, , Germany

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Klinikum Chemnitz gGmbH

Chemnitz, , Germany

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Universitatsklinikum Carl Gustav Carus

Dresden, , Germany

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Kreiskrankenhaus

Ebersberg, , Germany

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Universitaetsklinikum Essen

Essen, , Germany

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Elisabeth-Krankenhaus

Essen, , Germany

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Staedtische Kliniken Esslingen

Esslingen am Neckar, , Germany

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Onkologie Bethanien

Frankfurt, , Germany

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Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

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Staedtische Kliniken Frankfurt am Main - Hoechst

Frankfurt, , Germany

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Universitaetsfrauenklinik Freiburg

Freiburg im Breisgau, , Germany

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Franziskus Hospital Hardenberg

Georgsmarienhütte, , Germany

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Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

Greifswald, , Germany

Site Status

Universitaetsklinikum Halle

Halle, , Germany

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Henriettenstiftung Frauenklinik

Hanover, , Germany

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Medizinische Hochschule Hannover

Hanover, , Germany

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St. Vincentius - Kliniken

Karlsruhe, , Germany

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Klinikum Kassel

Kassel, , Germany

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University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

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Kreiskrankenhaus Lahr

Lahr, , Germany

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Kreiskrankenhaus Leonberg - Frauenklinik

Leonberg, , Germany

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Asklepios Klinik Lich

Lich, , Germany

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St. Vincenz Hospital Limburg

Limburg, , Germany

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Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

Lübeck, , Germany

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Staedtisches Klinikum Lueneburg

Lüneburg, , Germany

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Klinik St. Marienstift Magdeburg

Magdeburg, , Germany

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St. Vincenz und Elisabeth Hospital

Mainz, , Germany

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Universitaetsklinikum Giessen und Marburg GmbH - Marburg

Marburg, , Germany

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Klinikum Minden

Minden, , Germany

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I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen

Munich, , Germany

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Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

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Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

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Staedtisches Klinikum Neunkirchen gGmbH

Neunkirchen, , Germany

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Lukaskrankenhaus Neuss

Neuss, , Germany

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Klinikum Offenback GmbH

Offenbach, , Germany

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Saint Vincenz-Krankenhaus Paderborn

Paderborn, , Germany

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Klinikum Dorothea Christiane Erxleben - Quedlingburg

Quedlinburg, , Germany

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Krankenhaus St. Elisabeth - Ravensburg

Ravensburg, , Germany

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St. Marien - Krankenhaus Siegen GMBH

Siegen, , Germany

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Kliniken Landkreis Sigmaringen GMBH

Sigmaringen, , Germany

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Robert-Bosch-Krankenhaus

Stuttgart, , Germany

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Marienhospital Stuttgart

Stuttgart, , Germany

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Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, , Germany

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Dr. Horst-Schmidt-Kliniken

Wiesbaden, , Germany

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Marien-Hospital Witten

Witten, , Germany

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Klinikum der Stadt Wolfsburg

Wolfsburg, , Germany

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Praxis Fuer Haemotologie Und Internistischer Onkologie

Wuppertal, , Germany

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Norwegian Radium Hospital

Oslo, , Norway

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North Devon District Hospital

Barnstaple, England, United Kingdom

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Broomfield Hospital

Broomfield, England, United Kingdom

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Queen's Hospital

Burton-on-Trent, England, United Kingdom

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Addenbrooke's Hospital

Cambridge, England, United Kingdom

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Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, United Kingdom

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Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

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Queen Elizabeth Hospital

Gateshead, England, United Kingdom

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St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, United Kingdom

Site Status

Princess Royal Hospital at Hull and East Yorkshire NHS Trust

Hull, England, United Kingdom

Site Status

Ipswich Hospital

Ipswich, England, United Kingdom

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Airedale General Hospital

Keighley, England, United Kingdom

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Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

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University College of London Hospitals

London, England, United Kingdom

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Guy's Hospital

London, England, United Kingdom

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St. George's Hospital

London, England, United Kingdom

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Hammersmith Hospital

London, England, United Kingdom

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Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, United Kingdom

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Christie Hospital

Manchester, England, United Kingdom

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Queen Elizabeth The Queen Mother Hospital

Margate, England, United Kingdom

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Clatterbridge Centre for Oncology

Merseyside, England, United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, England, United Kingdom

Site Status

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

Northampton General Hospital

Northampton, England, United Kingdom

Site Status

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, England, United Kingdom

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Nottingham City Hospital

Nottingham, England, United Kingdom

Site Status

Churchill Hospital

Oxford, England, United Kingdom

Site Status

Derriford Hospital

Plymouth, England, United Kingdom

Site Status

Dorset Cancer Centre

Poole Dorset, England, United Kingdom

Site Status

Portsmouth Oncology Centre at Saint Mary's Hospital

Portsmouth Hants, England, United Kingdom

Site Status

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

Royal Shrewsbury Hospital

Shrewsbury, England, United Kingdom

Site Status

Stoke Mandeville Hospital

Shrewsbury, England, United Kingdom

Site Status

Wexham Park Hospital

Slough, Berkshire, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Staffordshire General Hospital

Stafford, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Great Western Hospital

Swindon, England, United Kingdom

Site Status

Royal Cornwall Hospital

Truro, Cornwall, England, United Kingdom

Site Status

Yeovil District Hospital

Yeovil - Somerset, England, United Kingdom

Site Status

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast, Northern Ireland, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Ninewells Hospital

Dundee, Scotland, United Kingdom

Site Status

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Site Status

Ysbyty Gwynedd

Bangor, Wales, United Kingdom

Site Status

South West Wales Cancer Institute

Swansea, Wales, United Kingdom

Site Status

Countries

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Australia France Germany Norway United Kingdom

References

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Dhillon S. Bevacizumab combination therapy: for the first-line treatment of advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Drugs. 2012 May 7;72(7):917-30. doi: 10.2165/11208940-000000000-00000.

Reference Type BACKGROUND
PMID: 22515620 (View on PubMed)

Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stahle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. doi: 10.1056/NEJMoa1103799.

Reference Type RESULT
PMID: 22204725 (View on PubMed)

Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type DERIVED
PMID: 37185961 (View on PubMed)

Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep 23;11(10):719-25. doi: 10.1038/nrc3144.

Reference Type DERIVED
PMID: 21941283 (View on PubMed)

Other Identifiers

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CDR0000548777

Identifier Type: REGISTRY

Identifier Source: secondary_id

EUDRACT-2005-003929-22

Identifier Type: -

Identifier Source: secondary_id

ISRCTN91273375

Identifier Type: -

Identifier Source: secondary_id

ROCHE-MREC-ICON7

Identifier Type: -

Identifier Source: secondary_id

EU-20730

Identifier Type: -

Identifier Source: secondary_id

MREC-06/MRE02/52

Identifier Type: -

Identifier Source: secondary_id

MREC-ICON7

Identifier Type: -

Identifier Source: org_study_id