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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Mario Negri Institute for Pharmacological Research
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT01706120
First received: October 10, 2012
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: Bevacizumab
Drug: Paclitaxel
Drug: Carboplatin
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • progression free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]
  • worst grade toxicity per patient [ Time Frame: evaluated every 3 weeks up to 15 month ] [ Designated as safety issue: Yes ]
    according to Common Toxicity Criteria for Adverse Events v. 4.03

  • number of patients taking oral antidiabetic therapy [ Time Frame: at baseline ] [ Designated as safety issue: No ]
  • number of patients taking antithrombotic therapy [ Time Frame: at baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: October 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01706120

Locations
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
Ospedale Cannizzaro
Catania, Italy
Azienda Ospedaliera Garibaldi Nesimadi Catania
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
IRCCS San Martino IST
Genova, Italy
E.O. Ospedali Galliera
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 Nazionale Tumori
MIlano, Italy
Istituto Europeo di Oncologia
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, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Mario Negri Institute for Pharmacological Research
Investigators
Principal Investigator: Sandro Pignata, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Nicoletta Colombo, M.D. European Institute of Oncology
Principal Investigator: Francesco Perrone, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Gennaro Daniele, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Roldano Fossati, M.D. Mario Negri Institute
Principal Investigator: Ciro Gallo, M.D. Second University of Naples
Principal Investigator: Irene Floriani, Ph.D. Mario Negri Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01706120     History of Changes
Other Study ID Numbers: MITO-16 - MANGO-OV2, 2012-003043-29
Study First Received: October 10, 2012
Last Updated: April 10, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
prognostic factors
biologic factors
clinical factors
routine clinical practice

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014