Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer

NCT ID: NCT01802749

Last Updated: 2023-03-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 406 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2023-12-31

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.

Conditions

Recurrent Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Carboplatin

Intervention Type: DRUG

pegylated liposomal doxorubicin

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Chemotherapy and 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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Carboplatin

Intervention Type: DRUG

pegylated liposomal doxorubicin

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Interventions

Bevacizumab

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Carboplatin

Intervention Type: DRUG

pegylated liposomal doxorubicin

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Other Intervention Names

Avastin; Caelyx

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: collaborator

National Cancer Institute, Naples

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandro Pignata, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Nicoletta Colombo, M.D.

Role: PRINCIPAL_INVESTIGATOR

European Institute of Oncology

Francesco Perrone, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Gennaro Daniele, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Roldano Fossati, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mario Negri Institute

Ciro Gallo, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Campania Luigi Vanvitelli

Irene Floriani, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mario Negri Institute

Locations

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-Mandé, , France

GHPSO

Senlis, , France

Centre de Radiothèrapie - Clinique Sainte-Anne

Strasbourg, , France

Clinique des Dentellières,

Valenciennes, , France

Institut de Cancérologie Gustave Roussy

Villejuif, , France

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, , Greece

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

Milan, , Italy

Istituto Nazionale Tumori

Milan, , 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

Padua, , 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 Universitario Gemelli Università Cattolica del Sacro Cuore

Roma, , Italy

Policlinico Università Campus Biomedico

Roma, , Italy

Ospedale di Sondrio

Sondrio, , Italy

A.O. Ordine Mauriziano

Torino, , Italy

A.O. di Udine S. Maria della Misericordia

Udine, , Italy

Centre Hospitalier Princesse Grace

Monaco, , Monaco

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

Lucerne, , Switzerland

Kantonsspital

Münsterlingen, , Switzerland

Kantonsspital

Olten, , Switzerland

Klinische Forschung Onkologie

Sankt Gallen, , Switzerland

Kantonsspital

Winterthur, , Switzerland

Countries

France; Greece; Italy; Monaco; Switzerland

References

Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type: DERIVED

PMID: 37185961 (View on PubMed)

Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO-OV2/ENGOT-ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. doi: 10.1016/S1470-2045(20)30637-9.

Reference Type: DERIVED

PMID: 33539744 (View on PubMed)

Arend R, Westin SN, Coleman RL. Decision analysis for secondline maintenance treatment of platinum sensitive recurrent ovarian cancer: a review. Int J Gynecol Cancer. 2020 May;30(5):684-694. doi: 10.1136/ijgc-2019-001041. Epub 2020 Feb 19.

Reference Type: DERIVED

PMID: 32079709 (View on PubMed)

Other Identifiers

2012-004362-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ENGOT-ov 17

Identifier Type: OTHER

Identifier Source: secondary_id

MITO-16 -MANGO-OV2b

Identifier Type: -

Identifier Source: org_study_id