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

Ovarian Cancer Clinical Trial

— MITO16/MANGO-2  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01706120
• Other study ID #: MITO-16 - MANGO-OV2
• Secondary ID: 2012-003043-29
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 2012
• Est. completion date: December 2024

Study information

• Verified date: March 2023
• Source: National Cancer Institute, Naples
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Bevacizumab
• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 22 cycles
• Paclitaxel
• Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks up to 6 cycles
• Carboplatin
• Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles

Locations

Country	Name	City	State
Italy	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	Milano
Italy	Istituto Nazionale Tumori	MIlano
Italy	Ospedale San Raffaele	Milano
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	Padova
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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute, Naples	Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	expression of soluble and tissutal biomarkers		measured at baseline, at completion of chemotherapy, at disease progression or bevacizumab completion up to 15 monthsfor each patient
Secondary	progression free survival		one year
Secondary	overall survival		three years
Secondary	worst grade toxicity per patient	according to Common Toxicity Criteria for Adverse Events v. 4.03	evaluated every 3 weeks up to 15 month
Secondary	number of patients taking oral antidiabetic therapy		at baseline
Secondary	number of patients taking antithrombotic therapy		at baseline