A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer

Global Study to Assess the Addition of Bevacizumab to Carboplatin and Paclitaxel as Front-line Treatment of Epithelial Ovarian Cancer, Fallopian Tube Carcinoma or Primary Peritoneal Carcinoma

This open-label, non-comparative, multi-center study will assess the safety profile and efficacy of Avastin (bevacizumab) when added to carboplatin and paclitaxel therapy in participants with epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. Participants will receive 15 milligrams/kilogram (mg/kg) Avastin intravenously (IV) on Day 1 of every cycle for up to 36 cycles of 3 weeks each, carboplatin (area under the plasma concentration-time curve [AUC] 5-6 mg/ml/min) on Day 1 every 3 weeks for a maximum of 8 cycles and paclitaxel 175 milligram per square meter (mg/m^2) on Day 1 every 3 weeks or 80 mg/m^2 every week for a maximum of 8 cycles. The anticipated time on study drug will be 108 weeks or until disease progression or unacceptable toxicity.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Bevacizumab; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 1021
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1199ACI
  • Buenos Aires, Argentina, C1280AEB
  • Buenos Aires, Argentina, C1426ANZ
  • Rosario, Argentina, S2002KDS
  • Tucuman, Argentina, T4000IAK
• Austria
  • Graz, Austria, 8020
  • Graz, Austria, 8036
  • Innsbruck, Austria, 6020
  • Ried-innkreis, Austria, 4910
  • Salzburg, Austria, 5020
  • Steyr, Austria, 4400
  • Villach, Austria, 9500
  • Wien, Austria, 1130
  • Wien, Austria, 1090
• Brazil
  • BA
    • Salvador, BA, Brazil, 41950-610
  • CE
    • Fortaleza, CE, Brazil, 60125-120
  • GO
    • Goiania, GO, Brazil, 74605-070
  • PR
    • Curitiba, PR, Brazil, 80530-010
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20230-130
  • RS
    • Porto Alegre, RS, Brazil, 90430-090
    • Porto Alegre, RS, Brazil, 90020-090
  • SP
    • Piracicaba, SP, Brazil, 13419-155
    • Sao Paulo, SP, Brazil, 01246-000
    • Sao Paulo, SP, Brazil, 01308-050
    • Sao Paulo, SP, Brazil, 01317-000
    • Sao Paulo, SP, Brazil, 01509-010
• Bulgaria
  • Sofia, Bulgaria, 1756
  • Varna, Bulgaria, 9010
  • Veliko Tarnovo, Bulgaria, 5000
• Canada
  • Quebec, Canada, G1R 3S1
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M5G 2M9
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
• Denmark
  • Aalborg, Denmark, 9000
  • Roskilde, Denmark, 4000
  • Vejle, Denmark, 7100
• Egypt
  • Cairo, Egypt, 11555
  • Tanta, Egypt
• Estonia
  • Tallinn, Estonia, 11312
  • Tallinn, Estonia, 13419
  • Tartu, Estonia, 50406
• France
  • Amiens, France, 80090
  • Bordeaux, France, 33076
  • Brest, France, 29200
  • Caen, France, 14076
  • Clermont Ferrand, France, 63011
  • Grenoble, France, 38028
  • Lille, France, 59020
  • Lyon, France, 69373
  • Marseille, France, 13273
  • Mougins, France, 06250
  • Paris, France, 75970
  • Paris, France, 75908
  • Paris, France, 75651
  • Paris, France, 75674
  • Paris, France, 75231
  • Paris, France, 75571
  • Reims CEDEX, France, 51056
  • Strasbourg, France, 67065
  • Toulouse, France, 31059
  • Villejuif, France, 94805
• Greece
  • Athens, Greece, 11527
  • Athens, Greece, 115 28
  • Athens, Greece, 145 64
  • Heraklion, Crete, Greece, 71110
  • Larissa, Greece, 41 110
  • Patras, Greece, 265 00
  • Thessaloniki, Greece, 56429
• Hong Kong
  • Hong Kong, Hong Kong
  • Hong Kong, Hong Kong, 852
• Hungary
  • Budapest, Hungary, 1125
  • Budapest, Hungary, 1122
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7624
  • Szeged, Hungary, 6720
• India
  • Bangalore, India, 560017
  • Bangalore, India, 560054
  • Hyderabad, India, 650034
  • Jaipur, India, 302013
  • Kochi, India, 682304
  • New Delhi, India, 110029
  • Pune, India, 411004
• Ireland
  • Dublin, Ireland, 7
• Israel
  • Afula, Israel, 18101
  • Beer Sheva, Israel, 8410101
  • Haifa, Israel, 34362
  • Haifa, Israel, 31096
  • Holon, Israel, 58100
  • Jerusalem, Israel, 91120-01
  • Jerusalem, Israel, 9372212
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49100
  • Ramat Gan, Israel, 52621
  • Rehovot, Israel, 7610001
  • Tel Aviv, Israel, 64239-06
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
    • Meldola, Emilia-Romagna, Italy, 47014
  • Lazio
    • Roma, Lazio, Italy, 00128
    • Roma, Lazio, Italy, 00157
  • Liguria
    • Genova, Liguria, Italy, 16128
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
    • Milano, Lombardia, Italy, 20162
    • Milano, Lombardia, Italy, 20141
    • Monza, Lombardia, Italy, 20052
    • Saronno, Lombardia, Italy, 21047
  • Piemonte
    • Novara, Piemonte, Italy, 28100
    • Torino, Piemonte, Italy, 10126
    • Torino, Piemonte, Italy, 10128
  • Sicilia
    • Palermo, Sicilia, Italy, 90146
  • Toscana
    • Firenze, Toscana, Italy, 50139
    • Pisa, Toscana, Italy, 56126
  • Umbria
    • Perugia, Umbria, Italy, 06123
    • Terni, Umbria, Italy, 05100
• Kuwait
  • Shuwaikh, Kuwait, 70653
• Latvia
  • Daugavpils, Latvia, 5417
  • Riga, Latvia, LV-1002
  • Riga, Latvia, LV 1079
• Lithuania
  • Kaunas, Lithuania, 50009
  • Klaipeda, Lithuania, 92288
  • Vilnius, Lithuania, 08660
• Macedonia, The Former Yugoslav Republic of
  • Bitola, Macedonia, The Former Yugoslav Republic of, 7000
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
• Mexico
  • Distrito Federal, Mexico, 14080
  • Oaxaca, Mexico, 68000
  • Toluca, Mexico, 50180
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
  • Amsterdam, Netherlands, 1091 AC
  • Apeldoorn, Netherlands, 7334 DZ
  • Blaricum, Netherlands, 1261 AN
  • Breda, Netherlands, 4819 EV
  • Capelle a/d IJssel, Netherlands, NL 2900 AR
  • Den Haag, Netherlands, 2545 CH
  • Den Haag, Netherlands, 2512 VA
  • Deventer, Netherlands, 7416 SE
  • Dordrecht, Netherlands, 3318 AT
  • Eindhoven, Netherlands, 5623 EJ
  • Leidschendam, Netherlands, 2262 BA
  • Rotterdam, Netherlands, 3045 PM
  • Sittard-Geleen, Netherlands, 6162 BG
  • Utrecht, Netherlands, 3582 KE
• Poland
  • Bydgoszcz, Poland, 85-796
  • Warszawa, Poland, 03-242
• Portugal
  • Porto, Portugal, 4200-072
• Romania
  • Bucuresti, Romania, 022328
  • Cluj Napoca, Romania, 400015
  • Iasi, Romania, 700106
• Russian Federation
  • Barnaul, Russian Federation, 656049
  • Moscow, Russian Federation, 115478
  • Obninsk, Kaluzhskaya Region, Russian Federation, 249034
  • Saint-Petersburg, Russian Federation, 197022
  • Stavropol, Russian Federation, 355045
  • UFA, Russian Federation, 450054
• Saudi Arabia
  • Dammam, Saudi Arabia, 31444
• Serbia
  • Belgrade, Serbia, 11000
  • Nis, Serbia, 18000
• Slovakia
  • Bratislava, Slovakia, 833 10
  • Kosice, Slovakia, 04001
• Slovenia
  • Ljubljana, Slovenia, 1000
  • Maribor, Slovenia, 2000
• South Africa
  • Durban, South Africa, 4058
  • Johannesburg, South Africa, 2193
  • Sandton, South Africa, 2196
• Spain
  • Albacete, Spain, 02006
  • Alicante, Spain, 3010
  • Badajoz, Spain, 06080
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08906
  • Barcelona, Spain, 08017
  • Burgos, Spain, 09006
  • Caceres, Spain, 10003
  • Castellon, Spain, 12002
  • Ciudad Real, Spain, 13005
  • Cordoba, Spain, 14004
  • Girona, Spain, 17007
  • Granada, Spain, 18014
  • Guadalajara, Spain, 19002
  • Jaen, Spain, 23007
  • La Coruña, Spain, 15006
  • Lugo, Spain, 27003
  • Madrid, Spain, 28040
  • Madrid, Spain, 28041
  • Madrid, Spain, 28007
  • Madrid, Spain, 28222
  • Madrid, Spain, 28033
  • Madrid, Spain, 28002
  • Madrid, Spain, 28050
  • Malaga, Spain, 29010
  • Malaga, Spain, 29011
  • Navarra, Spain, 31008
  • Salamanca, Spain, 37007
  • Segovia, Spain, 40002
  • Sevilla, Spain, 41014
  • Sevilla, Spain, 41009
  • Toledo, Spain, 45004
  • Valencia, Spain, 46017
  • Valencia, Spain, 46026
  • Valencia, Spain, 46009
  • Valencia, Spain, 46015
  • Valladolid, Spain, 47010
  • Zaragoza, Spain, 50009
  • Alicante
    • Elda, Alicante, Spain, 03600
  • Asturias
    • Oviedo, Asturias, Spain, 33011
  • Badajoz
    • Llerena (Badajoz), Badajoz, Spain, 06900
  • Barcelona
    • Manresa, Barcelona, Spain, 08243
  • Cadiz
    • Cádiz, Cadiz, Spain, 11009
    • Jerez de La Frontera, Cadiz, Spain, 11407
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20080
    • San Sebastian de Los Reyes, Guipuzcoa, Spain, 28702
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07014
    • Palma de Mallorca, Islas Baleares, Spain, 07198
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35020
  • Madrid
    • Leganes, Madrid, Spain, 28911
  • Tarragona
    • Reus, Tarragona, Spain, 43204
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
    • Santa Cruz de Tenerife, Tenerife, Spain, 38010
  • Valencia
    • San Juan, Valencia, Spain, 03550
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
    • Bilbao, Vizcaya, Spain, 48013
• Sweden
  • Eskilstuna, Sweden, 63188
  • Falun, Sweden, 79182
  • Karlstad, Sweden, 65185
  • Umeå, Sweden
  • Uppsala, Sweden, 75185
  • Örebro, Sweden, 701 85
• Switzerland
  • Aarau, Switzerland, 5001
  • Baden, Switzerland, 5405
  • Bellinzona, Switzerland, 6500
  • Bern, Switzerland, 3010
  • Genève 14, Switzerland, 1211
  • Zürich, Switzerland, 8091
• Taiwan
  • Taipei City, Taiwan, 110
  • Taipei City, Taiwan, 112
  • Taoyuan Hsien, Taiwan, 333
• Turkey
  • Ankara, Turkey, 06500
  • Ankara, Turkey, 06230
  • Diyarbakir, Turkey, 10000
  • Istanbul, Turkey, 34390
• Uruguay
  • Montevideo, Uruguay, 11600

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed epithelial ovarian carcinoma, fallopian tube carcinoma, primary peritoneal carcinoma or clear cell carcinoma or carcinosarcoma. Participants with recurrent ovarian cancer who have been previously treated with surgery alone for their early stage disease are eligible.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1 or 2
• Life expectancy greater than or equal to (>=3) months

Exclusion Criteria:

• Participants with non-epithelial ovarian cancer, ovarian tumors with low malignant potential (i.e., borderline tumors), or synchronous primary endometrial carcinoma
• Previous systemic therapy for ovarian cancer. Prior neo-adjuvant chemotherapy is allowed
• Planned intraperitoneal cytotoxic chemotherapy
• Radiotherapy within 28 days of Day 1, Cycle 1
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to first dose of Avastin
• History or evidence of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=1 arterial thromboembolic event or Grade >=3 venous thromboembolic event within 6 months prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bevacizumab + Paclitaxel + Carboplatin; Participants will receive bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol defined disease progression or until unacceptable toxicity (whichever occurred first). Participants will receive paclitaxel 175 mg/m^2 IV on Day 1 every 3 weeks or 80 mg/m^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol defined disease progression, or unacceptable toxicity (whichever occurred first).

Drug: Paclitaxel; 175 mg/m^2 on Day 1 every 3 weeks or at a dose of 80 mg/m^2 every week for a minimum of 4 cycles and not more than 8 cycles or until disease progression or unacceptable toxicity, whichever occurs first; Drug: Bevacizumab; 15 mg/kg intravenously on Day 1 of every cycle for up to 36 cycles of 3 weeks each or until disease progression or unacceptable toxicity, whichever occurs first; Other Names: Avastin; Drug: Carboplatin; AUC 5-6 mg/ml/min on Day 1 every 3 weeks for a minimum of 4 cycles and not more than 8 cycles or until disease progression or unacceptable toxicity, whichever occurs first

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Adverse Event (AE)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time between the date of first administration of any study treatment and the date of first documented protocol-defined disease progression (that is [i.e.], radiologically by Response Evaluation Criteria In Solid Tumors [RECIST], clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. Kaplan-Meier estimation was used for median time to PFS.	Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years
Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0	Best overall response (BOR) according to RECIST Version 1.0 was categorized as: CR, PR, progressive disease (PD), stable disease (SD). CR: disappearance of all target lesions and non-target lesions. PR: >=30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions. PD: Natural progression or deterioration of the malignancy under study (including new sites of metastasis). SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Participants with a BOR of CR and PR were defined as responders, while participants with a BOR of SD, PD, or unable to assess were defined as non-responders.	Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks (Q26W) after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years
Percentage of Participants Achieving an Overall Response by 50% Carcinoma Antigen 125 (CA-125) Response Criteria	CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days. Overall response according to CA-125 was only evaluated for participants with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the upper limit of normal (ULN).	3 days prior to Day 1 of every cycle, then every 6 weeks (Q6W) during the first year, every 3 months (Q3M) in the second and third year, every 6 months (Q6M) in the fourth year of the study (until data cutoff 07 December 2014, up to 4 years)
Percentage of Participants Achieving an Overall Response by RECIST Version 1.0 and/or 50% CA-125 Response Criteria	Overall response was only evaluated for participants who were evaluable according to RECIST v1.0 with a measurable disease at baseline and/or according to CA-125 with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the ULN. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions). CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days.	RECIST: Day 1, at end of Cycles 3 and 6, then every 6 cycles, at bevacizumab cessation, Q26W after cessation; CA-125: 3 days before Day 1 of every cycle, then Q6W(1st year), Q3M(2nd-3rd year), Q6M(4th year); until data cutoff 07Dec2014, up to 4 years
Duration of Objective Response (DOR)	DOR was defined as the time from the first documented response (CR or PR per RECIST v1.0), to the first documented protocol-defined disease progression (i.e., radiologically by RECIST, clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions). Disease progression: Natural progression or deterioration of the malignancy under study (including new sites of metastasis).	Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years
Overall Survival (OS)	OS was defined as the time from the date of the first administration of any study treatment to the date of death, regardless of the cause of death. Participants without the event of death were censored at the last date in the study, defined as the latest date of the following: the date of first administration of study treatment, date of last study treatment, date of last visit, or date last known to be alive. Kaplan-Meier estimation was used for OS.	First administration of any study treatment until death or data cutoff 07 December 2014, up to 4 years
Biological Progression-free Interval	Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for participants with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for participants with elevated CA-125 pre-treatment and initial normalization of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per participant on 2 occasions at least 1 week apart (for participants with elevated CA-125 pre-treatment which never normalized).	3 days prior to Day 1 of every cycle, then every 6 weeks during the first year, every 3 months in the second and third year, every 6 months in the fourth year of the study (until data cutoff 07 December 2014, up to 4 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Oza AM, Selle F, Davidenko I, Korach J, Mendiola C, Pautier P, Chmielowska E, Bamias A, DeCensi A, Zvirbule Z, Gonzalez-Martin A, Hegg R, Joly F, Zamagni C, Gadducci A, Martin N, Robb S, Colombo N. Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study. Int J Gynecol Cancer. 2017 Jan;27(1):50-58. doi: 10.1097/IGC.0000000000000836.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: November 10, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Estimate): June 10, 2016
• Last Update Submitted That Met QC Criteria: May 3, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: MO22923; 2010-019525-34 (EudraCT Number)