Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer
MITO16MANGO2b
Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line
3 other identifiers
interventional
406
5 countries
82
Brief Summary
Bevacizumab has been found to prolong progression free survival in first line, and more recently, in second line treatment for platinum sensitive ovarian cancer patients who had not received prior treatment with bevacizumab. Recently reported data suggest that patients with colon cancer who receive bevacizumab in more than one line of therapy (beyond progression) have better results. In ovarian cancer, the role of bevacizumab administered in both first and second-line therapies needs to be defined. This study aims to evaluate whether administering bevacizumab in combination with chemotherapy in second-line therapy to patients with recurrent ovarian cancer who have received first-line bevacizumab will be more effective than chemotherapy alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2013
Longer than P75 for phase_3
82 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 27, 2013
CompletedFirst Posted
Study publicly available on registry
March 1, 2013
CompletedStudy Start
First participant enrolled
November 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2023
CompletedMarch 24, 2023
March 1, 2023
10.1 years
February 27, 2013
March 23, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
progression free survival
assessed by local Investigator
12 months
Secondary Outcomes (6)
overall survival
12 months
number of complete or partial responses
6 months
worst grade toxicity per patient
evaluated every 3 weeks up to 12 months
number of patients taking oral antidiabetic therapy
at baseline
number of patients taking antithrombotic therapy
at baseline
- +1 more secondary outcomes
Other Outcomes (2)
predictive clinical factors for efficacy of bevacizumab
12 months
correlation of baseline plasma biomarker expression and clinical outcome
12 months
Study Arms (2)
chemotherapy
ACTIVE COMPARATORCombination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
Chemotherapy and bevacizumab
EXPERIMENTALCombination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
Interventions
Eligibility Criteria
You may qualify if:
- Female patients ≥18 years of age.
- Patients with histologically confirmed epithelial ovarian or fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours
- Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
- Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
- ECOG (Eastern Cooperative Oncology Group Performance) Status of 0-2.
- Life expectancy of at least 12 weeks.
- Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements including blood samples for molecular analyses.
- Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available)
You may not qualify if:
- Cancer related
- Ovarian tumours with low malignant potential (i.e. borderline tumours)
- History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:
- stage ≤Ia
- no more than superficial myometrial invasion
- no lymphovascular invasion
- not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
- Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
- Prior current or planned treatment:
- More than one previous chemotherapy line
- Previous therapy with other anti-angiogenetic agents different from bevacizumab.
- Any prior radiotherapy to the pelvis or abdomen.
- Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose.Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (except for line patency, in which case international normalized ratio \[INR\] must be maintained below 1.5). Post operative prophylaxis with low molecular weight heparin sc is allowed.
- Current or recent (within 30 days of first study dosing) treatment with any other investigational drug.
- Laboratory:
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (82)
Centre Hospitalier d'Aix-en-Provence
Aix-en-Provence, France
Hôpital de la Côte Basque
Bayonne, France
Institut Bergoniè
Bordeaux, France
Hôpital Fleyriat
Bourg-en-Bresse, France
Centre François Baclesse
Caen, France
Centre Hospitalier Intercommunal de Créteil
Créteil, France
Centre d'Oncologie et de Radiothérapie
Dijon, France
Centre Georges Francois Leclerc
Dijon, France
Centre Hospitalier du Mans
Le Mans, France
Centre Hospitalier Universitaire Dupuytren
Limoges, France
Centre Léon Bérard
Lyon, France
Clinique de la Sauvegarde
Lyon, France
Hôpital Nord
Marseille, France
Hôpital Saint-Joseph
Marseille, France
Clinique Claude Bernard
Metz, France
Centre Azuréen de Cancérologie
Mougins, France
Centre Hospitalier Général de Pau
Paris, France
Hopital Cochin
Paris, France
Hôpital des Diaconesses
Paris, France
Hôpital Tenon
Paris, France
Centre Hospitalier Général de Pau
Pau, France
Centre Hospitalier de la Région d'Annecy
Pringy, France
Institut Jean Godinot
Reims, France
Hopital Renè Huguenin, Institut Curie
Saint-Cloud, France
Hôpital Inter Armées de Begin (HIA Begin),
Saint-Mandé, France
GHPSO
Senlis, France
Centre de Radiothèrapie - Clinique Sainte-Anne
Strasbourg, France
Clinique des Dentellières,
Valenciennes, France
Institut de Cancérologie Gustave Roussy
Villejuif, France
Anticancer Hospital Agio Savvas
Athens, Greece
General Hospital of Athens Alexandra
Athens, Greece
General Oncology Hospital Agii Anargiri
Athens, Greece
General Hospital of Thessaloniki Papageorgiou
Thessaloniki, Greece
Centro di Riferimento Oncologico
Aviano, Italy
A.O. G. Rummo
Benevento, Italy
Spedali Civili Università di Brescia
Brescia, Italy
Ospedale Senatore Antonio Perrino
Brindisi, Italy
Fondazione del Piemonte per l'Oncologia IRCCS
Candiolo, Italy
Osp. Cannizzaro
Catania, Italy
Ospedale Civile di Faenza
Faenza, Italy
I.R.C.C.S. San Martino IST
Genova, Italy
Ospedale Galliera
Genova, Italy
ASL 5 Spezzino Ospedale Felettino
La Spezia, Italy
A.O. Vito Fazzi
Lecce, Italy
Ospedale Manzoni di Lecco
Lecco, Italy
Istituto Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy
Istituto Europeo di Oncologia
Milan, Italy
Istituto Nazionale Tumori
Milan, Italy
U.L.S.S. 13
Mirano, Italy
A.O.U. Federico II
Napoli, Italy
A.O.U. Seconda Università di Napoli
Napoli, Italy
Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
Napoli, Italy
Ist. Sacro Cuore Don Calabria
Negrar, Italy
NO AOU Maggiore della Carità
Novara, Italy
Istituto Oncologico Veneto
Padua, Italy
Casa di Cura La Maddalena
Palermo, Italy
Osp Silvestrini
Perugia, Italy
Ospedale Santa Chiara
Pisa, Italy
A.O. S. Maria degli Angeli
Pordenone, Italy
AO ASL 4
Prato, Italy
Ospedale S. Maria delle Croci AUSL di Ravenna
Ravenna, Italy
Arcispedale S. Maria Nuova
Reggio Emilia, Italy
Ospedale Civile Rimini
Rimini, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli
Roma, Italy
Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
Roma, Italy
Policlinico Università Campus Biomedico
Roma, Italy
Ospedale di Sondrio
Sondrio, Italy
A.O. Ordine Mauriziano
Torino, Italy
A.O. di Udine S. Maria della Misericordia
Udine, Italy
Centre Hospitalier Princesse Grace
Monaco, Monaco
Zentrum fùr Onkologie/ Hamat. und Transf
Aarau, Switzerland
Universitatsspital,Frauenklinik
Basel, Switzerland
IOSI
Bellinzona, Switzerland
Klinik Engeried
Bern, Switzerland
Kantonsspital
Chur, Switzerland
Kantonsspital
Frauenfeld, Switzerland
HUG Breast Center
Geneva, Switzerland
Kantonsspital
Lucerne, Switzerland
Kantonsspital
Münsterlingen, Switzerland
Kantonsspital
Olten, Switzerland
Klinische Forschung Onkologie
Sankt Gallen, Switzerland
Kantonsspital
Winterthur, Switzerland
Related Publications (3)
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.
PMID: 37185961DERIVEDPignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO-OV2/ENGOT-ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. doi: 10.1016/S1470-2045(20)30637-9.
PMID: 33539744DERIVEDArend R, Westin SN, Coleman RL. Decision analysis for secondline maintenance treatment of platinum sensitive recurrent ovarian cancer: a review. Int J Gynecol Cancer. 2020 May;30(5):684-694. doi: 10.1136/ijgc-2019-001041. Epub 2020 Feb 19.
PMID: 32079709DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sandro Pignata, M.D., Ph.D.
National Cancer Institute, Naples
- PRINCIPAL INVESTIGATOR
Nicoletta Colombo, M.D.
European Institute of Oncology
- PRINCIPAL INVESTIGATOR
Francesco Perrone, M.D., Ph.D.
National Cancer Institute, Naples
- PRINCIPAL INVESTIGATOR
Gennaro Daniele, M.D., Ph.D.
National Cancer Institute, Naples
- PRINCIPAL INVESTIGATOR
Roldano Fossati, M.D.
Mario Negri Institute
- PRINCIPAL INVESTIGATOR
Ciro Gallo, M.D.
University of Campania Luigi Vanvitelli
- PRINCIPAL INVESTIGATOR
Irene Floriani, Ph.D.
Mario Negri Institute
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 27, 2013
First Posted
March 1, 2013
Study Start
November 1, 2013
Primary Completion
December 1, 2023
Study Completion
December 1, 2023
Last Updated
March 24, 2023
Record last verified: 2023-03