Evaluation of Optimal Treatment Duration of Bevacizumab Combination With Standard Chemotherapy in Patients With Ovarian Cancer

NCT ID: NCT01462890

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 927 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2021-12-31

Brief Summary

The purpose of this study is to determine whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months.

Detailed Description

Determination whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months

Conditions

Genital Diseases, Female; Ovarian Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Arm

Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.

Group Type: OTHER

Bevacizumab

Intervention Type: BIOLOGICAL

15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 22 vs cycle 44

Paclitaxel

Intervention Type: DRUG

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Carboplatin

Intervention Type: DRUG

AUC 5, iv on day 1 every 3 weeks for 6 cycles

specialized pathology review (Germany only)

Intervention Type: OTHER

before randomization

Research Arm

Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Carboplatin

Intervention Type: DRUG

AUC 5, iv on day 1 every 3 weeks for 6 cycles

specialized pathology review (Germany only)

Intervention Type: OTHER

before randomization

Interventions

Bevacizumab

15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 22 vs cycle 44

Intervention Type: BIOLOGICAL

Paclitaxel

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Carboplatin

AUC 5, iv on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

specialized pathology review (Germany only)

before randomization

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements
• Primary diagnosis is confirmed by specialized pathology review (Germany only)
• Females aged ≥ 18 years
• Histologically confirmed, newly diagnosed

• Epithelial ovarian carcinoma
• Fallopian tube carcinoma
• Primary peritoneal carcinoma AND FIGO stage IIb - IV (all grades and all histological types)
• Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement. There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate or possible will still be eligible providing

• the patient has a histological diagnosis and
• debulking surgery prior to disease progression is not foreseen
• Patients must be able to commence cytotoxic chemotherapy within 8 weeks of cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if the investigator decides to start chemotherapy within 4 weeks of surgery.
• ECOG 0-2
• Life expectancy > 3 months
• Adequate bone marrow function (within 14 days prior to randomization)

• ANC ≥ 1.5 x 10^9/L
• PLT ≥ 100 x 10^9/L
• Hb ≥ 9 g/dL (can be post-transfusion)
• Adequate coagulation parameters (within 14 days prior to randomization)

• Patients not receiving anticoagulant medication who have an INR ≤ 1.5 and an aPTT ≤ 1.5 x ULN
• The use of full-dose oral or par-enteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization.
• Adequate liver function (within 14 days prior to randomization)

• Serum bilirubin ≤ 1.5 x ULN
• Serum transaminases ≤ 2.5 x ULN
• Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24 hour urine must demonstrate ≤ 1 g of protein in 24 hours
• Adequate postoperative GFR > 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula are sufficient)

Exclusion Criteria

• Non-epithelial origin of the ovary, the fallopian tube or the peritoneum
• Borderline tumours (tumours of low malignant potential) and FIGO stage Ia - IIa tumours
• Planned intraperitoneal cytotoxic chemotherapy
• Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
• Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.
• Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance
• Uncontrolled hypertension (sustained elevation of BP systolic > 150mmHg and/or diastolic > 100mmHg despite antihypertensive therapy)
• Any previous radiotherapy to the abdomen or pelvis
• Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab
• History or clinical suspicion of brain metastases or spinal cord compression. CT/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.
• History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy e.g. uncontrolled seizures
• Previous Cerebro-Vascular Accident (CVA), Transient Ischaemic Attack (TIA) or Sub-Arachnoid Haemorrhage (SAH) within 6 months prior to randomization
• 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 study duration and at least 6 months afterwards
• Pregnant or lactating women
• Treatment with other investigational agents, or participation in another clinical trial testing a drug within the past 4 weeks before start of therapy concomitantly with this trial
• Malignancies other than ovarian cancer within 5 years prior to randomization, except for adequately treated

• carcinoma in situ of the cervix
• and/or basal cell skin cancer
• and/or non-melanomatous skin cancer
• carcinoma in situ of the breast
• and/or early endometrial carcinoma as specified below. Patients may have received previous adjuvant chemotherapy for other malignancies e.g. breast or colorectal carcinoma if diagnosed over 5 years ago with no evidence of subsequent recurrence.
• Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met

• Disease stage FIGO stage ≤ IA (tumour invades less than one half of the myometrium)
• Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell products or other recombinant human or humanised antibodies
• Non healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations
• History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
• Clinically significant cardiovascular disease, including

• Myocardial infarction or unstable angina within 6 months of randomization
• NYHA ≥ Grade 2 Congestive Heart Failure (CHF)
• Poorly controlled cardiac arrhythmia despite medication (patients with rate-controlled atrial fibrillation are eligible)
• Grade ≥ 3 peripheral vascular disease (i.e. symptomatic and interfering with activities of daily living requiring repair or revision)
• Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day
• Pre-existing sensory or motor neuropathy ≥ Grade 2
• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

ARCAGY/ GINECO GROUP

OTHER

Sponsor Role: collaborator

Nordic Society of Gynaecological Oncology - Clinical Trials Unit

OTHER

Sponsor Role: collaborator

AGO Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacobus Pfisterer, MD PhD

Role: STUDY_CHAIR

AGO Study Group

Locations

Aalborg, , Denmark

Copenhagen, , Denmark

Herlev, , Denmark

Kuopio, , Finland

Oulu, , Finland

Tampere, , Finland

Turku, , Finland

Angers, , France

Besançon, , France

Blois, , France

Bordeaux, , France

Caen, , France

Cahors, , France

Clamart, , France

Clermont-Ferrand, , France

Créteil, , France

Dax, , France

Draguignan, , France

Grenoble, , France

Limoges, , France

Lyon, , France

Mougins, , France

Nancy, , France

Nantes, , France

Nice, , France

Nîmes, , France

Orléans, , France

Paris, , France

Pau, , France

Plérin, , France

Poitiers, , France

Quimper, , France

Reims, , France

Rouen, , France

Saint-Herblain, , France

Strasbourg, , France

Toulouse, , France

Vandœuvre-lès-Nancy, , France

Vannes, , France

Villejuif, , France

Aachen, , Germany

Arnsberg, , Germany

Aschaffenburg, , Germany

Augsburg, , Germany

Bad Homburg, , Germany

Berlin, , Germany

Bochum, , Germany

Bonn, , Germany

Bottrop, , Germany

Brandenburg, , Germany

Bremen, , Germany

Chemnitz, , Germany

Coburg, , Germany

Cologne, , Germany

Deggendorf, , Germany

Dessau, , Germany

Dresden, , Germany

Düsseldorf, , Germany

Ebersberg, , Germany

Eggenfelden, , Germany

Erlangen, , Germany

Essen, , Germany

Esslingen am Neckar, , Germany

Flensburg, , Germany

Frankfurt/M., , Germany

Freiburg im Breisgau, , Germany

Fürstenfeldbruck, , Germany

Fürth, , Germany

Georgsmarienhütte, , Germany

Gera, , Germany

Göttingen, , Germany

Greifswald, , Germany

Gütersloh, , Germany

Halle, , Germany

Hamburg, , Germany

Hanau, , Germany

Hanover, , Germany

Heidelberg, , Germany

Henstedt-Ulzburg, , Germany

Hildesheim, , Germany

Jena, , Germany

Kaiserslautern, , Germany

Karlsruhe, , Germany

Kassel, , Germany

Kiel, , Germany

Krefeld, , Germany

Lich, , Germany

Limburg, , Germany

Lübeck, , Germany

Lüneburg, , Germany

Magdeburg, , Germany

Mainz, , Germany

Mannheim, , Germany

Marburg, , Germany

Minden, , Germany

München, , Germany

Neumarkt, , Germany

Neuss, , Germany

Nordhausen, , Germany

Offenbach, , Germany

Offenburg, , Germany

Oldenburg, , Germany

Osnabrück, , Germany

Ravensburg, , Germany

Regensburg, , Germany

Reutlingen, , Germany

Rosenheim, , Germany

Rostock, , Germany

Rottweil, , Germany

Saalfeld, , Germany

Salzgitter, , Germany

Schwäbisch Hall, , Germany

Schweinfurt, , Germany

Sigmaringen, , Germany

Solingen, , Germany

Stralsund, , Germany

Stuttgart, , Germany

Torgau, , Germany

Trier, , Germany

Tübingen, , Germany

Ulm, , Germany

Viersen, , Germany

Wiesbaden, , Germany

Witten, , Germany

Wolfsburg, , Germany

Worms, , Germany

Bergen, , Norway

Oslo, , Norway

Trondheim, , Norway

Falun, , Sweden

Uppsala, , Sweden

Countries

Denmark; Finland; France; Germany; Norway; Sweden

References

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)

Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Luck HJ, Emons G, Meier W, Gropp-Meier M, Schroder W, de Gregorio N, Hilpert F, Harter P. Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial. J Clin Oncol. 2023 Feb 1;41(4):893-902. doi: 10.1200/JCO.22.01010. Epub 2022 Nov 4.

Reference Type: DERIVED

PMID: 36332161 (View on PubMed)

Other Identifiers

AGO-OVAR 17

Identifier Type: -

Identifier Source: org_study_id