Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab (MITO16/MANGO-2)

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

A MULTICENTER STUDY IN PATIENTS WITH STAGE III-IV EPITHELIAL OVARIAN CANCER TREATED WITH CARBOPLATIN/PACLITAXEL WITH BEVACIZUMAB: CLINICAL AND BIOLOGICAL PROGNOSTIC FACTORS

The addition of bevacizumab to first-line chemotherapy has been shown to improve progression free survival for patients with ovarian cancer. The purpose of this study is to explore the potential role of clinical and biologic factors in identifying those patients who benefit most from this combined therapy in terms of progression free and overall survival.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

MITO-16 - MANGO-OV2 is a single-arm, open-label, non-comparative, multicenter, phase IV study. Patients will receive a combination of bevacizumab, paclitaxel and carboplatin as first line treatment (in-label dose and scheduling). This is an exploratory study attempting to identify potential prognostic clinical factors(such as hypertension) and prognostic biologic factors. Overall, 2 types of biomarkers are considered. Dynamic biomarkers are those expressing the changing nature of the disease in relation to the treatment or simply the tumour progression, these are typically not inherited. Genetic biomarkers are typically inherited and are expression of some characteristics potentially able to interfere with the treatment effect (i.e. Pharmacogenomics).

The safety of this regimen in routine clinical practice will also be described.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

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

  • Italy
      • Alessandria, Italy
        • A.S.O. SS Antonio e Biagio e Cesare Arrigo
      • Aviano, Italy
        • Centro Di Riferimento Oncologico
      • Benevento, Italy
        • Ospedale Fatebenefratelli
      • Brescia, Italy
        • Spedali Civili - Università di Brescia
      • Brindisi, Italy
        • Ospedale Senatore Antonio Perrino
      • Candiolo, Italy
        • Fondazione del Piemonte per l'Oncologia
      • Carpi, Italy
        • Ospedale Ramazzini di Carpi /Ospedale di Mirandola
      • Catania, Italy
        • Azienda Ospedaliera Garibaldi Nesimadi Catania
      • Catania, Italy
        • Ospedale Cannizzaro
      • Catanzaro, Italy
        • Ospedale Mater Domini
      • Faenza, Italy
        • Ospedale Civile di Faenza
      • Fano, Italy
        • Ospedale Santa Croce
      • Ferrara, Italy
        • A.O.U. Arcispedale Sant'Anna di Ferrara
      • Frosinone, Italy
        • Ospedale Fabrizio Spaziani di Frosinone / Osp. SS Trinità di Sora
      • Genova, Italy
        • E.O. Ospedali Galliera
      • Genova, Italy
        • IRCCS San Martino IST
      • Guastalla, Italy
        • Ospedale di Guastalla
      • Lecco, Italy
        • Ospedale A. Manzoni
      • Legnago, Italy
        • Ospedale Mater Salutis
      • MIlano, Italy
        • Istituto Nazionale Tumori
      • Manerbio, Italy
        • Presidio Ospedaliero Manerbio
      • Mantova, Italy
        • A.O. C. Poma
      • Meldola, Italy
        • Istituto Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy
        • Istituto Europeo di Oncologia
      • Milano, Italy
        • Ospedale San Raffaele
      • Mirano, Italy
        • U.L.S.S. 13
      • Modena, Italy
        • A.O.U. Policlinico Modena
      • Monza, Italy
        • Ospedale S. Gerardo
      • Napoli, Italy
        • Istituto Nazionale dei Tumori
      • Napoli, Italy
        • AOU Policlinico Federico II
      • Negrar, Italy
        • Istituto Sacro Cuore Don Calabria
      • Padova, Italy
        • Istituto Oncologico Veneto
      • Pavia, Italy
        • Fondazione IRCCS S. Matteo
      • Perugia, Italy
        • Ospedale Silvestrini
      • Pisa, Italy
        • Ospedale Santa Chiara
      • Pordenone, Italy
        • A.O. Santa Maria degli Angeli
      • Ravenna, Italy
        • Ospedale S. Maria Delle Croci
      • Reggio Emilia, Italy
        • Arcispedale S. Maria nuova
      • Rimini, Italy
        • Ospedale degli Infermi / Ospedale Civile
      • Roma, Italy
        • Istituto Regina Elena
      • Roma, Italy
        • Ospedale S. Giovanni Calibita Fatebenefratelli
      • Roma, Italy
        • Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
      • Torino, Italy
        • A.O. Ordine Mauriziano
      • Torino, Italy
        • A.O.U. OIRM-S. Anna
      • Trieste, Italy
        • ASS N 1 Triestina
      • Udine, Italy
        • A.O. di Udine S. Maria delle Misericordia
      • Varese, Italy
        • Ospedale Del Ponte

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 carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours Or Recurrent early stage epithelial ovarian or fallopian tube carcinoma treated with surgery alone.
  • FIGO stage IIIB & C or IV
  • ECOG 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.
  • Availability of tumour samples for molecular analyses

Exclusion Criteria:

Cancer related

  • Ovarian tumours with low malignant potential (i.e. borderline tumours)
  • Previous systemic anti-cancer therapy for advanced ovarian cancer.
  • History or evidence of brain metastases or spinal cord compression.

  • 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.

Other-treatment related

  • Any prior radiotherapy to the pelvis or abdomen.
  • Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose or planned (In this case the patient can be enrolled but the administration of bevacizumab should be omitted at first cycle).
  • Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes (except for central venous access 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 another investigational drug.

Laboratory related

  • Inadequate bone marrow function: ANC: <1.5 x 109/l, or platelet count <100 x 109/l 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 xULN or
    • INR >1.5

  • Inadequate liver function, defined as:

    • serum (total) bilirubin >1.5 x the upper limit of normal (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
  • Proteinuria >1g in a 24-hour urine collection (to be performed only among patients who showed a ≥3+ at urine dipstick).

Patient related

  • Pregnant or lactating patients.
  • History or evidence of thrombotic or hemorrhagic 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 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 fascial 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: First-line chemotherapy with bevacizumab
  • Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks for up to 22 cycles
  • Paclitaxel 175 mg/m2 on Day 1 every 3 weeks for up to 6 cycles
  • Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles
Drug: Bevacizumab
• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 22 cycles
Other Names:
  • Avastin
Drug: Paclitaxel
• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 6 cycles
Drug: Carboplatin
• Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
expression of soluble and tissutal biomarkers
Time Frame: measured at baseline, at completion of chemotherapy, at disease progression or bevacizumab completion up to 15 monthsfor each patient
measured at baseline, at completion of chemotherapy, at disease progression or bevacizumab completion up to 15 monthsfor each patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: three years
three years
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: one year
one year
worst grade toxicity per patient
Time Frame: evaluated every 3 weeks up to 15 month
according to Common Toxicity Criteria for Adverse Events v. 4.03
evaluated every 3 weeks up to 15 month

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

October 1, 2012

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

October 10, 2012

First Submitted That Met QC Criteria

October 10, 2012

First Posted (Estimate)

October 15, 2012

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-OV2
  • 2012-003043-29 (EudraCT Number)

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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