Clinical trial NCT01706120: Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ovarian Cancer
Keywords: prognostic factors
biologic factors
clinical factors
routine clinical practice
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2012-10-15
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: expression of soluble and tissutal biomarkers
timeFrame: measured at baseline, at completion of chemotherapy, at disease progression or bevacizumab completion up to 15 monthsfor each patient
Secondary outcomes:
measure: progression free survival
timeFrame: one year
measure: overall survival
timeFrame: three years
measure: worst grade toxicity per patient
timeFrame: evaluated every 3 weeks up to 15 month
measure: number of patients taking oral antidiabetic therapy
timeFrame: at baseline
measure: number of patients taking antithrombotic therapy
timeFrame: at baseline
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.S.O. SS Antonio e Biagio e Cesare Arrigo
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
city: Benevento
country: Italy
facility: Ospedale Fatebenefratelli
city: Brescia
country: Italy
facility: Spedali Civili - Università di Brescia
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia
city: Carpi
country: Italy
facility: Ospedale Ramazzini di Carpi /Ospedale di Mirandola
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibaldi Nesimadi Catania
city: Catania
country: Italy
facility: Ospedale Cannizzaro
city: Catanzaro
country: Italy
facility: Ospedale Mater Domini
city: Faenza
country: Italy
facility: Ospedale Civile di Faenza
city: Fano
country: Italy
facility: Ospedale Santa Croce
city: Ferrara
country: Italy
facility: A.O.U. Arcispedale Sant'Anna di Ferrara
city: Frosinone
country: Italy
facility: Ospedale Fabrizio Spaziani di Frosinone / Osp. SS Trinità di Sora
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
city: Genova
country: Italy
facility: IRCCS San Martino IST
city: Guastalla
country: Italy
facility: Ospedale di Guastalla
city: Lecco
country: Italy
facility: Ospedale A. Manzoni
city: Legnago
country: Italy
facility: Ospedale Mater Salutis
city: Manerbio
country: Italy
facility: Presidio Ospedaliero Manerbio
city: Mantova
country: Italy
facility: A.O. C. Poma
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: MIlano
country: Italy
facility: Istituto Nazionale Tumori
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Mirano
country: Italy
facility: U.L.S.S. 13
city: Modena
country: Italy
facility: A.O.U. Policlinico Modena
city: Monza
country: Italy
facility: Ospedale S. Gerardo
city: Napoli
country: Italy
facility: AOU Policlinico Federico II
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori
city: Negrar
country: Italy
facility: Istituto Sacro Cuore Don Calabria
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Pavia
country: Italy
facility: Fondazione IRCCS S. Matteo
city: Perugia
country: Italy
facility: Ospedale Silvestrini
city: Pisa
country: Italy
facility: Ospedale Santa Chiara
city: Pordenone
country: Italy
facility: A.O. Santa Maria degli Angeli
city: Ravenna
country: Italy
facility: Ospedale S. Maria delle Croci
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Rimini
country: Italy
facility: Ospedale degli Infermi / Ospedale Civile
city: Roma
country: Italy
facility: Istituto Regina Elena
city: Roma
country: Italy
facility: Ospedale S. Giovanni Calibita Fatebenefratelli
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
city: Torino
country: Italy
facility: A.O. Ordine Mauriziano
city: Torino
country: Italy
facility: A.O.U. OIRM-S. Anna
city: Trieste
country: Italy
facility: ASS N 1 Triestina
city: Udine
country: Italy
facility: A.O. di Udine S. Maria delle Misericordia
city: Varese
country: Italy
facility: Ospedale del Ponte
Study officials:
affiliation: National Cancer Institute, Naples
name: Sandro Pignata, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: European Institute of Oncology
name: Nicoletta Colombo, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Gennaro Daniele, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mario Negri Institute
name: Roldano Fossati, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Campania Luigi Vanvitelli
name: Ciro Gallo, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mario Negri Institute
name: Irene Floriani, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.