Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer

Recurrent Ovarian Cancer Clinical Trial

— MITO16MANGO2b  

Official title:

Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01802749
• Other study ID #: MITO-16 -MANGO-OV2b
• Secondary ID: 2012-004362-17EN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2013
• Est. completion date: December 2023

Study information

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

Clinical Trial Summary

Bevacizumab has been found to prolong progression free survival in first line, and more recently, in second line treatment for platinum sensitive ovarian cancer patients who had not received prior treatment with bevacizumab. Recently reported data suggest that patients with colon cancer who receive bevacizumab in more than one line of therapy (beyond progression) have better results. In ovarian cancer, the role of bevacizumab administered in both first and second-line therapies needs to be defined. This study aims to evaluate whether administering bevacizumab in combination with chemotherapy in second-line therapy to patients with recurrent ovarian cancer who have received first-line bevacizumab will be more effective than chemotherapy alone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 406
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• 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 or fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours
• Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
• Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
• ECOG (Eastern Cooperative Oncology Group 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 including blood samples for molecular analyses.
• Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available) Exclusion Criteria: Cancer related
• Ovarian tumours with low malignant potential (i.e. borderline tumours)
• 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.

Prior current or planned treatment:

• More than one previous chemotherapy line
• Previous therapy with other anti-angiogenetic agents different from bevacizumab.
• Any prior radiotherapy to the pelvis or abdomen.
• Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose.Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (except for line 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 any other investigational drug.

Laboratory:

• Inadequate bone marrow function: ANC (absolute neutrophil count): <1500/mm3, or platelet count <100,000/mm3 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 x upper limit of normal (ULN) or
• INR (international normalized ratio) >1.5
• Inadequate liver function, defined as:
• serum (total) bilirubin >1.5 x 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
• urine dipstick for proteinuria >2+. Patients with = 1+ proteinuria at baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate =1g of protein in their 24-hour urine collection.

Prior or concomitant conditions or procedures:

• History or evidence of brain metastases or spinal cord compression.
• Pregnant or lactating females.
• History or evidence of thrombotic or haemorrhagic 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, or with signs of impending bowel obstruction 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 facial 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
• Hypersensitivity
• Ovarian Neoplasms
• Recurrent Ovarian Cancer

Intervention

Drug:
• Bevacizumab

• Paclitaxel

• Carboplatin

• pegylated liposomal doxorubicin

• Gemcitabine

Locations

Country	Name	City	State
France	Centre Hospitalier d'Aix-en-Provence	Aix-en-Provence
France	Hôpital de la Côte Basque	Bayonne
France	Institut Bergoniè	Bordeaux
France	Hôpital Fleyriat	Bourg-en-Bresse
France	Centre François Baclesse	Caen
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Centre d'Oncologie et de Radiothérapie	Dijon
France	Centre Georges Francois Leclerc	Dijon
France	Centre Hospitalier du Mans	Le Mans
France	Centre Hospitalier Universitaire Dupuytren	Limoges
France	Centre Léon Bérard	Lyon
France	Clinique de la Sauvegarde	Lyon
France	Hôpital Nord	Marseille
France	Hôpital Saint-Joseph	Marseille
France	Clinique Claude Bernard	Metz
France	Centre Azuréen de Cancérologie	Mougins
France	Centre Hospitalier Général de Pau	Paris
France	Hopital Cochin	Paris
France	Hôpital des Diaconesses	Paris
France	Hôpital Tenon	Paris
France	Centre Hospitalier Général de Pau	Pau
France	Centre Hospitalier de la Région d'Annecy	Pringy
France	Institut Jean Godinot	Reims
France	Hopital Renè Huguenin, Institut Curie	Saint Cloud
France	Hôpital Inter Armées de Begin (HIA Begin),	Saint Mande
France	GHPSO	Senlis
France	Centre de Radiothèrapie - Clinique Sainte-Anne	Strasbourg
France	Clinique des Dentellières,	Valenciennes
France	Institut de Cancérologie Gustave Roussy	Villejuif
Greece	Anticancer Hospital Agio Savvas	Athens
Greece	General Hospital of Athens Alexandra	Athens
Greece	General Oncology Hospital Agii Anargiri	Athens
Greece	General Hospital of Thessaloniki Papageorgiou	Thessaloniki
Italy	Centro di Riferimento Oncologico	Aviano
Italy	A.O. G. Rummo	Benevento
Italy	Spedali Civili Università di Brescia	Brescia
Italy	Ospedale Senatore Antonio Perrino	Brindisi
Italy	Fondazione del Piemonte per l'Oncologia IRCCS	Candiolo
Italy	Osp. Cannizzaro	Catania
Italy	Ospedale Civile di Faenza	Faenza
Italy	I.R.C.C.S. San Martino IST	Genova
Italy	Ospedale Galliera	Genova
Italy	ASL 5 Spezzino Ospedale Felettino	La Spezia
Italy	A.O. Vito Fazzi	Lecce
Italy	Ospedale Manzoni di Lecco	Lecco
Italy	Istituto Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori	Milano
Italy	U.L.S.S. 13	Mirano
Italy	A.O.U. Federico II	Napoli
Italy	A.O.U. Seconda Università di Napoli	Napoli
Italy	Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico	Napoli
Italy	Ist. Sacro Cuore Don Calabria	Negrar
Italy	NO AOU Maggiore della Carità	Novara
Italy	Istituto Oncologico Veneto	Padova
Italy	Casa di Cura La Maddalena	Palermo
Italy	Osp Silvestrini	Perugia
Italy	Ospedale Santa Chiara	Pisa
Italy	A.O. S. Maria degli Angeli	Pordenone
Italy	AO ASL 4	Prato
Italy	Ospedale S. Maria delle Croci AUSL di Ravenna	Ravenna
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	Ospedale Civile Rimini	Rimini
Italy	Ospedale S. Giovanni Calibita Fatebenefratelli	Roma
Italy	Policlinico Università Campus Biomedico	Roma
Italy	Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore	Roma
Italy	Ospedale di Sondrio	Sondrio
Italy	A.O. Ordine Mauriziano	Torino
Italy	A.O. di Udine S. Maria della Misericordia	Udine
Monaco	Centre Hospitalier Princesse Grace	Monaco
Switzerland	Zentrum fùr Onkologie/ Hamat. und Transf	Aarau
Switzerland	Universitatsspital,Frauenklinik	Basel
Switzerland	IOSI	Bellinzona
Switzerland	Klinik Engeried	Bern
Switzerland	Kantonsspital	Chur
Switzerland	Kantonsspital	Frauenfeld
Switzerland	HUG Breast Center	Geneva
Switzerland	Kantonsspital	Luzern
Switzerland	Kantonsspital	Munsterlingen
Switzerland	Kantonsspital	Olten
Switzerland	Klinische Forschung Onkologie	St. Gallen
Switzerland	Kantonsspital	Winterthur

Sponsors (2)

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

Countries where clinical trial is conducted

France,  Greece,  Italy,  Monaco,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	predictive clinical factors for efficacy of bevacizumab		12 months
Other	correlation of baseline plasma biomarker expression and clinical outcome		12 months
Primary	progression free survival	assessed by local Investigator	12 months
Secondary	overall survival		12 months
Secondary	number of complete or partial responses	according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	6 months
Secondary	worst grade toxicity per patient	according to Common Toxicity Criteria for Adverse Events v. 4.03	evaluated every 3 weeks up to 12 months
Secondary	number of patients taking oral antidiabetic therapy		at baseline
Secondary	number of patients taking antithrombotic therapy		at baseline
Secondary	progression free survival	as measured by independent central review	12 months