Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer (MITO16MANGO2b)

March 23, 2023 updated by: National Cancer Institute, Naples

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

406

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Aix-en-Provence, France
        • Centre Hospitalier d'Aix-en-Provence
      • Bayonne, France
        • Hopital de la cote Basque
      • Bordeaux, France
        • Institut Bergonie
      • Bourg-en-Bresse, France
        • Hôpital Fleyriat
      • Caen, France
        • Centre Francois Baclesse
      • Créteil, France
        • Centre Hospitalier Intercommunal de Créteil
      • Dijon, France
        • Centre Georges François Leclerc
      • Dijon, France
        • Centre d'oncologie et de radiothérapie
      • Le Mans, France
        • Centre Hospitalier du Mans
      • Limoges, France
        • Centre Hospitalier Universitaire Dupuytren
      • Lyon, France
        • Centre Léon Bérard
      • Lyon, France
        • Clinique de la Sauvegarde
      • Marseille, France
        • Hopital Nord
      • Marseille, France
        • Hôpital Saint-Joseph
      • Metz, France
        • Clinique Claude Bernard
      • Mougins, France
        • Centre Azuréen de Cancérologie
      • Paris, France
        • Hopital Cochin
      • Paris, France
        • Hopital Tenon
      • Paris, France
        • Centre Hospitalier Général de Pau
      • Paris, France
        • Hôpital des Diaconesses
      • Pau, France
        • Centre Hospitalier Général de Pau
      • Pringy, France
        • Centre hospitalier de la région d'Annecy
      • Reims, France
        • Institut Jean Godinot
      • Saint Cloud, France
        • HOPITAL RENE HUGUENIN, Institut Curie
      • Saint Mande, France
        • Hôpital Inter Armées de Begin (HIA Begin),
      • Senlis, France
        • GHPSO
      • Strasbourg, France
        • Centre de Radiothérapie - Clinique Sainte-Anne
      • Valenciennes, France
        • Clinique des Dentellières,
      • Villejuif, France
        • Institut de Cancérologie Gustave Roussy
  • Greece
      • Athens, Greece
        • Anticancer Hospital Agio Savvas
      • Athens, Greece
        • General Hospital of Athens Alexandra
      • Athens, Greece
        • General Oncology Hospital Agii Anargiri
      • Thessaloniki, Greece
        • General Hospital Of Thessaloniki Papageorgiou
  • Italy
      • Aviano, Italy
        • Centro di Riferimento Oncologico
      • Benevento, Italy
        • A.O. G. Rummo
      • Brescia, Italy
        • Spedali Civili Università di Brescia
      • Brindisi, Italy
        • Ospedale Senatore Antonio Perrino
      • Candiolo, Italy
        • Fondazione del Piemonte per l'Oncologia IRCCS
      • Catania, Italy
        • Osp. Cannizzaro
      • Faenza, Italy
        • Ospedale Civile di Faenza
      • Genova, Italy
        • I.R.C.C.S. San Martino IST
      • Genova, Italy
        • Ospedale Galliera
      • La Spezia, Italy
        • ASL 5 Spezzino Ospedale Felettino
      • Lecce, Italy
        • A.O. Vito Fazzi
      • Lecco, Italy
        • Ospedale Manzoni di Lecco
      • Meldola, Italy
        • Istituto Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy
        • Istituto Europeo di Oncologia
      • Milano, Italy
        • Istituto Nazionale Tumori
      • Mirano, Italy
        • U.L.S.S. 13
      • Napoli, Italy
        • A.O.U. Federico II
      • Napoli, Italy
        • A.O.U. Seconda Universita di Napoli
      • Napoli, Italy
        • Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
      • Negrar, Italy
        • Ist. Sacro Cuore Don Calabria
      • Novara, Italy
        • NO AOU Maggiore della Carità
      • Padova, Italy
        • Istituto Oncologico Veneto
      • Palermo, Italy
        • Casa di Cura La Maddalena
      • Perugia, Italy
        • Osp Silvestrini
      • Pisa, Italy
        • Ospedale Santa Chiara
      • Pordenone, Italy
        • A.O. S. Maria degli Angeli
      • Prato, Italy
        • AO ASL 4
      • Ravenna, Italy
        • Ospedale S. Maria delle Croci AUSL di Ravenna
      • Reggio Emilia, Italy
        • Arcispedale S. Maria nuova
      • Rimini, Italy
        • Ospedale Civile Rimini
      • Roma, Italy
        • Ospedale S. Giovanni Calibita Fatebenefratelli
      • Roma, Italy
        • Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
      • Roma, Italy
        • Policlinico Università Campus Biomedico
      • Sondrio, Italy
        • Ospedale di Sondrio
      • Torino, Italy
        • A.O. Ordine Mauriziano
      • Udine, Italy
        • A.O. di Udine S. Maria della Misericordia
  • Monaco
      • Monaco, Monaco
        • Centre Hospitalier Princesse Grace
  • Switzerland
      • Aarau, Switzerland
        • Zentrum fùr Onkologie/ Hamat. und Transf
      • Basel, Switzerland
        • Universitatsspital,Frauenklinik
      • Bellinzona, Switzerland
        • IOSI
      • Bern, Switzerland
        • Klinik Engeried
      • Chur, Switzerland
        • Kantonsspital
      • Frauenfeld, Switzerland
        • Kantonsspital
      • Geneva, Switzerland
        • HUG Breast Center
      • Luzern, Switzerland
        • Kantonsspital
      • Munsterlingen, Switzerland
        • Kantonsspital
      • Olten, Switzerland
        • Kantonsspital
      • St. Gallen, Switzerland
        • Klinische Forschung Onkologie
      • Winterthur, Switzerland
        • Kantonsspital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

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:

  • Inadequate bone marrow function: ANC (absolute neutrophil count): <1500/mm3, or platelet count <100,000/mm3 or Haemoglobin <9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl.

  • Inadequate coagulation parameters:

    • activated partial thromboplastin time (APTT) >1.5 x upper limit of normal (ULN) or
    • INR (international normalized ratio) >1.5

  • Inadequate liver function, defined as:

    • serum (total) bilirubin >1.5 x ULN for the institution
    • AST/SGOT or ALT/SGPT > 2.5 x ULN.

  • Inadequate renal function, defined as:

    • serum creatinine >2.0 mg/dl or >177 micromol/l
    • urine dipstick for proteinuria >2+. Patients with ≥ 1+ proteinuria at baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection.

Prior or concomitant conditions or procedures:

  • History or evidence of brain metastases or spinal cord compression.
  • Pregnant or lactating females.
  • History or evidence of thrombotic or haemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤6 months prior to the first study treatment).
  • Uncontrolled hypertension (sustained systolic >150 mm Hg and/or diastolic >100 mm Hg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including:
  • myocardial infarction or unstable angina within ≤6 months prior to the first study treatment
  • New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF)
  • serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
  • peripheral vascular disease ≥grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision).
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, or with signs of impending bowel obstruction within 6 months prior to the first study treatment.
  • Non-healing 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.
  • Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: chemotherapy

Combination 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.
Drug: Gemcitabine
Drug: Carboplatin
Drug: Paclitaxel
Drug: pegylated liposomal doxorubicin
Other Names:
  • Caelyx
Experimental: Chemotherapy and bevacizumab

Combination 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.
Drug: Gemcitabine
Drug: Carboplatin
Drug: Paclitaxel
Drug: Bevacizumab
Other Names:
  • Avastin
Drug: pegylated liposomal doxorubicin
Other Names:
  • Caelyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: 12 months
assessed by local Investigator
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: 12 months
12 months
number of complete or partial responses
Time Frame: 6 months
according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
6 months
worst grade toxicity per patient
Time Frame: evaluated every 3 weeks up to 12 months
according to Common Toxicity Criteria for Adverse Events v. 4.03
evaluated every 3 weeks up to 12 months
number of patients taking oral antidiabetic therapy
Time Frame: at baseline
at baseline
number of patients taking antithrombotic therapy
Time Frame: at baseline
at baseline
progression free survival
Time Frame: 12 months
as measured by independent central review
12 months

Other Outcome Measures

Outcome Measure
Time Frame
predictive clinical factors for efficacy of bevacizumab
Time Frame: 12 months
12 months
correlation of baseline plasma biomarker expression and clinical outcome
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute, Naples

Collaborators

Mario Negri Institute for Pharmacological Research

Investigators

  • Principal Investigator: Nicoletta Colombo, M.D., European Institute of Oncology
  • Principal Investigator: Roldano Fossati, M.D., Mario Negri Institute
  • Principal Investigator: Irene Floriani, Ph.D., Mario Negri Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

February 27, 2013

First Submitted That Met QC Criteria

February 28, 2013

First Posted (Estimate)

March 1, 2013

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 23, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MITO-16 -MANGO-OV2b
  • 2012-004362-17 (EudraCT Number)
  • ENGOT-ov 17 (Other Identifier: ENGOT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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