Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab

NCT ID: NCT01706120

Last Updated: 2023-03-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2024-12-31

Brief Summary

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.

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: OTHER

Bevacizumab

Intervention Type: DRUG

• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 22 cycles

Paclitaxel

Intervention Type: DRUG

• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 6 cycles

Carboplatin

Intervention Type: DRUG

• Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles

Interventions

Bevacizumab

• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 22 cycles

Intervention Type: DRUG

Paclitaxel

• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 6 cycles

Intervention Type: DRUG

Carboplatin

• Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

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.

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

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: collaborator

National Cancer Institute, Naples

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandro Pignata, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Nicoletta Colombo, M.D.

Role: PRINCIPAL_INVESTIGATOR

European Institute of Oncology

Francesco Perrone, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Gennaro Daniele, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Roldano Fossati, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mario Negri Institute

Ciro Gallo, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Campania Luigi Vanvitelli

Irene Floriani, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mario Negri Institute

Locations

A.S.O. SS Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Centro di Riferimento Oncologico

Aviano, , Italy

Ospedale Fatebenefratelli

Benevento, , Italy

Spedali Civili - Università di Brescia

Brescia, , Italy

Ospedale Senatore Antonio Perrino

Brindisi, , Italy

Fondazione del Piemonte per l'Oncologia

Candiolo, , Italy

Ospedale Ramazzini di Carpi /Ospedale di Mirandola

Carpi, , Italy

Azienda Ospedaliera Garibaldi Nesimadi Catania

Catania, , Italy

Ospedale Cannizzaro

Catania, , Italy

Ospedale Mater Domini

Catanzaro, , Italy

Ospedale Civile di Faenza

Faenza, , Italy

Ospedale Santa Croce

Fano, , Italy

A.O.U. Arcispedale Sant'Anna di Ferrara

Ferrara, , Italy

Ospedale Fabrizio Spaziani di Frosinone / Osp. SS Trinità di Sora

Frosinone, , Italy

E.O. Ospedali Galliera

Genova, , Italy

IRCCS San Martino IST

Genova, , Italy

Ospedale di Guastalla

Guastalla, , Italy

Ospedale A. Manzoni

Lecco, , Italy

Ospedale Mater Salutis

Legnago, , Italy

Presidio Ospedaliero Manerbio

Manerbio, , Italy

A.O. C. Poma

Mantova, , Italy

Istituto Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori

Milan, , Italy

Ospedale San Raffaele

Milan, , Italy

U.L.S.S. 13

Mirano, , Italy

A.O.U. Policlinico Modena

Modena, , Italy

Ospedale S. Gerardo

Monza, , Italy

AOU Policlinico Federico II

Napoli, , Italy

Istituto Nazionale dei Tumori

Napoli, , Italy

Istituto Sacro Cuore Don Calabria

Negrar, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Fondazione IRCCS S. Matteo

Pavia, , Italy

Ospedale Silvestrini

Perugia, , Italy

Ospedale Santa Chiara

Pisa, , Italy

A.O. Santa Maria degli Angeli

Pordenone, , Italy

Ospedale S. Maria delle Croci

Ravenna, , Italy

Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Ospedale degli Infermi / Ospedale Civile

Rimini, , Italy

Istituto Regina Elena

Roma, , Italy

Ospedale S. Giovanni Calibita Fatebenefratelli

Roma, , Italy

Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore

Roma, , Italy

A.O. Ordine Mauriziano

Torino, , Italy

A.O.U. OIRM-S. Anna

Torino, , Italy

ASS N 1 Triestina

Trieste, , Italy

A.O. di Udine S. Maria delle Misericordia

Udine, , Italy

Ospedale del Ponte

Varese, , Italy

Countries

Italy

References

Di Liello R, Arenare L, Raspagliesi F, Scambia G, Pisano C, Colombo N, Frezzini S, Tognon G, Artioli G, Gadducci A, Lauria R, Ferrero A, Cinieri S, De Censi A, Breda E, Scollo P, De Giorgi U, Lissoni AA, Katsaros D, Lorusso D, Salutari V, Cecere SC, Lapresa M, Nardin M, Bogani G, Distefano M, Greggi S, Gargiulo P, Schettino C, Gallo C, Daniele G, Califano D, Perrone F, Pignata S, Piccirillo MC. Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial. Int J Gynecol Cancer. 2021 Oct;31(10):1348-1355. doi: 10.1136/ijgc-2021-002786. Epub 2021 Aug 30.

Reference Type: DERIVED

PMID: 34462317 (View on PubMed)

Daniele G, Raspagliesi F, Scambia G, Pisano C, Colombo N, Frezzini S, Tognon G, Artioli G, Gadducci A, Lauria R, Ferrero A, Cinieri S, De Censi A, Breda E, Scollo P, De Giorgi U, Lissoni AA, Katsaros D, Lorusso D, Salutari V, Cecere SC, Zaccarelli E, Nardin M, Bogani G, Distefano M, Greggi S, Piccirillo MC, Fossati R, Giannone G, Arenare L, Gallo C, Perrone F, Pignata S. Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study. Int J Gynecol Cancer. 2021 Jun;31(6):875-882. doi: 10.1136/ijgc-2021-002434. Epub 2021 Apr 30.

Reference Type: DERIVED

PMID: 33931498 (View on PubMed)

Other Identifiers

2012-003043-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MITO-16 - MANGO-OV2

Identifier Type: -

Identifier Source: org_study_id