Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer
- Conditions
- Recurrent Ovarian Cancer
- Interventions
- Registration Number
- NCT01802749
- Lead Sponsor
- National Cancer Institute, Naples
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 406
- 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)
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy and bevacizumab pegylated liposomal doxorubicin Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn. chemotherapy pegylated liposomal doxorubicin Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days. chemotherapy Paclitaxel Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days. chemotherapy Gemcitabine Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days. chemotherapy Carboplatin Combination chemotherapy with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days; * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days. Chemotherapy and bevacizumab Bevacizumab Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn. Chemotherapy and bevacizumab Paclitaxel Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn. Chemotherapy and bevacizumab Gemcitabine Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn. Chemotherapy and bevacizumab Carboplatin Combination chemotherapy AND bevacizumab with ONE of the following regimens: * PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks; * GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L * PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks. Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.
- Primary Outcome Measures
Name Time Method progression free survival 12 months assessed by local Investigator
- Secondary Outcome Measures
Name Time Method overall survival 12 months number of complete or partial responses 6 months according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
worst grade toxicity per patient evaluated every 3 weeks up to 12 months according to Common Toxicity Criteria for Adverse Events v. 4.03
number of patients taking oral antidiabetic therapy at baseline number of patients taking antithrombotic therapy at baseline progression free survival 12 months as measured by independent central review
Trial Locations
- Locations (76)
IOSI
🇨🇭Bellinzona, Switzerland
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Osp Silvestrini
🇮🇹Perugia, Italy
Ospedale S. Maria delle Croci AUSL di Ravenna
🇮🇹Ravenna, Italy
Ospedale Civile Rimini
🇮🇹Rimini, Italy
Institut Bergoniè
🇫🇷Bordeaux, France
Clinique de la Sauvegarde
🇫🇷Lyon, France
Clinique Claude Bernard
🇫🇷Metz, France
Centre Azuréen de Cancérologie
🇫🇷Mougins, France
Centre Hospitalier Général de Pau
🇫🇷Pau, France
Hopital Cochin
🇫🇷Paris, France
GHPSO
🇫🇷Senlis, France
Hopital Renè Huguenin, Institut Curie
🇫🇷Saint Cloud, France
Centre Hospitalier d'Aix-en-Provence
🇫🇷Aix-en-Provence, France
Centre d'Oncologie et de Radiothérapie
🇫🇷Dijon, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Hospitalier Universitaire Dupuytren
🇫🇷Limoges, France
Hôpital de la Côte Basque
🇫🇷Bayonne, France
General Hospital of Athens Alexandra
🇬🇷Athens, Greece
General Oncology Hospital Agii Anargiri
🇬🇷Athens, Greece
General Hospital of Thessaloniki Papageorgiou
🇬🇷Thessaloniki, Greece
Centre Hospitalier de la Région d'Annecy
🇫🇷Pringy, France
Ospedale Galliera
🇮🇹Genova, Italy
A.O. Vito Fazzi
🇮🇹Lecce, Italy
Istituto Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
A.O.U. Federico II
🇮🇹Napoli, Italy
Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
🇮🇹Napoli, Italy
Centre de Radiothèrapie - Clinique Sainte-Anne
🇫🇷Strasbourg, France
Zentrum fùr Onkologie/ Hamat. und Transf
🇨🇭Aarau, Switzerland
Klinik Engeried
🇨🇭Bern, Switzerland
Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Ospedale Senatore Antonio Perrino
🇮🇹Brindisi, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
A.O. Ordine Mauriziano
🇮🇹Torino, Italy
Anticancer Hospital Agio Savvas
🇬🇷Athens, Greece
Centro di Riferimento Oncologico
🇮🇹Aviano, Italy
A.O. G. Rummo
🇮🇹Benevento, Italy
Spedali Civili Università di Brescia
🇮🇹Brescia, Italy
ASL 5 Spezzino Ospedale Felettino
🇮🇹La Spezia, Italy
NO AOU Maggiore della Carità
🇮🇹Novara, Italy
Casa di Cura La Maddalena
🇮🇹Palermo, Italy
A.O.U. Seconda Università di Napoli
🇮🇹Napoli, Italy
Ist. Sacro Cuore Don Calabria
🇮🇹Negrar, Italy
Ospedale Santa Chiara
🇮🇹Pisa, Italy
A.O. S. Maria degli Angeli
🇮🇹Pordenone, Italy
AO ASL 4
🇮🇹Prato, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli
🇮🇹Roma, Italy
Ospedale di Sondrio
🇮🇹Sondrio, Italy
A.O. di Udine S. Maria della Misericordia
🇮🇹Udine, Italy
Centre Hospitalier Princesse Grace
🇲🇨Monaco, Monaco
Universitatsspital,Frauenklinik
🇨🇭Basel, Switzerland
Policlinico Università Campus Biomedico
🇮🇹Roma, Italy
Hôpital Saint-Joseph
🇫🇷Marseille, France
Hôpital Fleyriat
🇫🇷Bourg-en-Bresse, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
Centre François Baclesse
🇫🇷Caen, France
Centre Hospitalier du Mans
🇫🇷Le Mans, France
Hôpital Nord
🇫🇷Marseille, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut Jean Godinot
🇫🇷Reims, France
Hôpital Inter Armées de Begin (HIA Begin),
🇫🇷Saint Mande, France
Hôpital Tenon
🇫🇷Paris, France
Hôpital des Diaconesses
🇫🇷Paris, France
Institut de Cancérologie Gustave Roussy
🇫🇷Villejuif, France
Clinique des Dentellières,
🇫🇷Valenciennes, France
Ospedale Civile di Faenza
🇮🇹Faenza, Italy
I.R.C.C.S. San Martino IST
🇮🇹Genova, Italy
Fondazione del Piemonte per l'Oncologia IRCCS
🇮🇹Candiolo, Italy
Osp. Cannizzaro
🇮🇹Catania, Italy
Ospedale Manzoni di Lecco
🇮🇹Lecco, Italy
Istituto Nazionale Tumori
🇮🇹Milano, Italy
U.L.S.S. 13
🇮🇹Mirano, Italy
Kantonsspital
🇨🇭Winterthur, Switzerland
Klinische Forschung Onkologie
🇨🇭St. Gallen, Switzerland
HUG Breast Center
🇨🇭Geneva, Switzerland