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

Ovarian Cancer Clinical Trial

Official title:

ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00483782
• Other study ID #: MREC-ICON7
• Secondary ID: CDR0000548777EUD
• Status: Completed
• Phase: Phase 3
• First received: June 6, 2007
• Last updated: August 9, 2013
• Start date: April 2006

Study information

• Verified date: April 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1520
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer

• Newly diagnosed disease

• Meets 1 of the following staging criteria:

• High-risk stage I or IIA disease (grade 3 disease or clear cell carcinoma only)

• Stage IIB-IV disease (all grades and all histological types)

• Must have undergone initial surgery (e.g., debulking cytoreductive surgery or a biopsy if the patient has stage IV disease) within the past 6 weeks

• Patients with stage IV disease for which initial surgical debulking was not appropriate are eligible provided the following criteria are met:

• 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)

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Biological:
• bevacizumab

Drug:
• carboplatin

• paclitaxel

Other:
• questionnaire administration

• study of socioeconomic and demographic variables

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital Cancer Centre	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Royal Women's Hospital	Carlton	Victoria
Australia	Mercy Hospital for Women	East Melbourne	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Cancer Therapy Centre at Liverpool Hospital	Liverpool	New South Wales
Australia	Sir Charles Gairdner Hospital - Perth	Perth	Western Australia
Australia	Prince of Wales Private Hospital	Randwick	New South Wales
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	Sydney Cancer Centre at Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Newcastle Mater Misericordiae Hospital	Waratah	New South Wales
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Wentworthville	New South Wales
Australia	Murray Valley Private Hospital and Cancer Treatment Centre	Wodonga	Victoria
France	Centre Paul Papin	Angers
France	Institut Sainte Catherine	Avignon
France	Clinique Tivoli	Bordeaux
France	Institut Bergonie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Centre Regional Francois Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Hopital Louis Pasteur	Colmar
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Institut Prive de Cancerologie	Grenoble
France	Hopital Andre Mignot	Le Chesnay
France	Centre Jean Bernard	Le Mans
France	Centre Leon Berard	Lyon
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre D'Oncologie De Gentilly	Nancy
France	Centre Catherine de Sienne	Nantes
France	Centre Regional Rene Gauducheau	Nantes-Saint Herblain
France	Hopital Cochin	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Tenon	Paris
France	Hotel Dieu de Paris	Paris
France	Institut Curie Hopital	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Henri Becquerel	Rouen
France	Clinique Armoricaine De Radiologie	Saint Brieuc
France	Centre Rene Huguenin	Saint Cloud
France	Hopital Universitaire Hautepierre	Strasbourg
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Evang. Waldkrankenhaus Spandau	Berlin
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Praxis Dres. F.& G. Doering	Bremen
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Kreiskrankenhaus	Ebersberg
Germany	Elisabeth-Krankenhaus	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Staedtische Kliniken Esslingen	Esslingen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Onkologie Bethanien	Frankfurt
Germany	Staedtische Kliniken Frankfurt am Main - Hoechst	Frankfurt
Germany	Universitaetsfrauenklinik Freiburg	Freiburg
Germany	Franziskus Hospital Hardenberg	Georgsmarienhuette
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Universitaetsklinikum Halle	Halle
Germany	Henriettenstiftung Frauenklinik	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	St. Vincentius - Kliniken	Karlsruhe
Germany	Klinikum Kassel	Kassel
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Kreiskrankenhaus Lahr	Lahr
Germany	Kreiskrankenhaus Leonberg - Frauenklinik	Leonberg
Germany	Asklepios Klinik Lich	Lich
Germany	St. Vincenz Hospital Limburg	Limburg
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck
Germany	Staedtisches Klinikum Lueneburg	Lueneburg
Germany	Klinik St. Marienstift Magdeburg	Magdeburg
Germany	St. Vincenz und Elisabeth Hospital	Mainz
Germany	Universitaetsklinikum Giessen und Marburg GmbH - Marburg	Marburg
Germany	Klinikum Minden	Minden
Germany	I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen	Munich
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Staedtisches Klinikum Neunkirchen gGmbH	Neunkirchen
Germany	Lukaskrankenhaus Neuss	Neuss
Germany	Klinikum Offenback GmbH	Offenbach
Germany	Saint Vincenz-Krankenhaus Paderborn	Paderborn
Germany	Klinikum Dorothea Christiane Erxleben - Quedlingburg	Quedlinburg
Germany	Krankenhaus St. Elisabeth - Ravensburg	Ravensburg
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Kliniken Landkreis Sigmaringen GMBH	Sigmaringen
Germany	Marienhospital Stuttgart	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Marien-Hospital Witten	Witten
Germany	Klinikum der Stadt Wolfsburg	Wolfsburg
Germany	Praxis Fuer Haemotologie Und Internistischer Onkologie	Wuppertal
Norway	Norwegian Radium Hospital	Oslo
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Broomfield Hospital	Broomfield	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Airedale General Hospital	Keighley	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Northampton General Hospital	Northampton	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Churchill Hospital	Oxford	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Portsmouth Oncology Centre at Saint Mary's Hospital	Portsmouth Hants	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Stoke Mandeville Hospital	Shrewsbury	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Staffordshire General Hospital	Stafford	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	South West Wales Cancer Institute	Swansea	Wales
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Yeovil District Hospital	Yeovil - Somerset	England

Sponsors (1)

Lead Sponsor	Collaborator
Medical Research Council

Countries where clinical trial is conducted

Australia,  France,  Germany,  Norway,  United Kingdom, 

References & Publications (2)

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. Review. — View Citation

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, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival			No
Secondary	Duration of overall survival			No
Secondary	Objective response rate			No
Secondary	Duration of response			No
Secondary	Biological progression-free interval as measured by increasing CA 125 levels			No
Secondary	Safety as measured by NCI CTAE version 3.0			Yes
Secondary	Quality of life			No
Secondary	Health economics			No