Ovarian CancerPhase 3NCT01239732
A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer
A Phase 3 study testing Paclitaxel, Bevacizumab and Carboplatin in people with Ovarian Cancer, run by Hoffmann-La Roche at 242 sites in 37 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Paclitaxel, Bevacizumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,021 participants
- Where
- 242 sitesin 37 countries
- Study dates
- Dec 2010to Mar 2015
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
242 sites in 37 countries.
242 sites in 37 countries
Spain58 sites
Study site
A Coruña, La Coruña, 15006
Study site
Albacete, Albacete, 02006
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Alicante, Alicante, 3010
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Badajoz, Badajoz, 06080
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Barakaldo, Vizcaya, 48903
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Barcelona, Barcelona, 08003
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Barcelona, Barcelona, 08017
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Barcelona, Barcelona, 08036
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Barcelona, Barcelona, 08906
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Bilbao, Vizcaya, 48013
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Burgos, Burgos, 09006
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Cáceres, Caceres, 10003
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Cadiz, Cadiz, 11009
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Castellon, Castellon, 12002
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Ciudad Real, Ciudad Real, 13005
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Córdoba, Cordoba, 14004
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Donostia / San Sebastian, Guipuzcoa, 20080
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Elda, Alicante, 03600
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Girona, Girona, 17007
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Granada, Granada, 18014
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Guadalajara, Guadalajara, 19002
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Jaén, Jaen, 23007
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Jerez de la Frontera, Cadiz, 11407
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Las Palmas de Gran Canaria, Las Palmas, 35020
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Leganés, Madrid, 28911
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Llerena (Badajoz), Badajoz, 06900
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Lugo, Lugo, 27003
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Madrid, Madrid, 28002
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Madrid, Madrid, 28007
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Madrid, Madrid, 28033
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Madrid, Madrid, 28040
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Madrid, Madrid, 28041
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Madrid, Madrid, 28050
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Madrid, Madrid, 28222
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Málaga, Malaga, 29010
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Málaga, Malaga, 29011
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Manresa, Barcelona, 08243
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Navarra, Navarre, 31008
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Oviedo, Principality of Asturias, 33011
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Palma de Mallorca, Balearic Islands, 07014
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Palma de Mallorca, Balearic Islands, 07198
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Reus, Tarragona, 43204
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Salamanca, Salamanca, 37007
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San Cristóbal de La Laguna, Tenerife, 38320
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San Juan, Valencia, 03550
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San Sebastián de los Reyes, Guipuzcoa, 28702
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Santa Cruz de Tenerife, Tenerife, 38010
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Santiago de Compostela, La Coruña, 15706
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Segovia, Segovia, 40002
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Seville, Sevilla, 41009
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Seville, Sevilla, 41014
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Toledo, Toledo, 45004
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Valencia, Valencia, 46009
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Valencia, Valencia, 46015
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Valencia, Valencia, 46017
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Valencia, Valencia, 46026
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Valladolid, Valladolid, 47010
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Zaragoza, Zaragoza, 50009
France20 sites
Study site
Amiens, 80090
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Bordeaux, 33076
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Brest, 29200
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Caen, 14076
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Clermont-Ferrand, 63011
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Grenoble, 38028
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Lille, 59020
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Lyon, 69373
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Marseille, 13273
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Mougins, 06250
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Paris, 75231
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Paris, 75571
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Paris, 75651
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Paris, 75674
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Paris, 75908
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Paris, 75970
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Reims, 51056
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Strasbourg, 67065
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Toulouse, 31059
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Villejuif, 94805
Italy19 sites
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Bologna, Emilia-Romagna, 40138
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Brescia, Lombardy, 25123
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Florence, Tuscany, 50139
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Genoa, Liguria, 16128
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Meldola, Emilia-Romagna, 47014
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Milan, Lombardy, 20141
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Milan, Lombardy, 20162
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Monza, Lombardy, 20052
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Naples, Campania, 80131
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Novara, Piedmont, 28100
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Palermo, Sicily, 90146
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Perugia, Umbria, 06123
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Pisa, Tuscany, 56126
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Rome, Lazio, 00128
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Rome, Lazio, 00157
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Saronno, Lombardy, 21047
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Terni, Umbria, 05100
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Turin, Piedmont, 10126
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Turin, Piedmont, 10128
Netherlands15 sites
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Alkmaar, 1815 JD
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Amsterdam, 1091 AC
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Apeldoorn, 7334 DZ
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Blaricum, 1261 AN
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Breda, 4819 EV
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Capelle aan den IJssel, NL 2900 AR
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Deventer, 7416 SE
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Dordrecht, 3318 AT
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Eindhoven, 5623 EJ
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Leidschendam, 2262 BA
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Rotterdam, 3045 PM
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Sittard-Geleen, 6162 BG
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The Hague, 2512 VA
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The Hague, 2545 CH
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Utrecht, 3582 KE
Brazil12 sites
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Curitiba, Paraná, 80530-010
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Fortaleza, Ceará, 60125-120
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Goiânia, Goiás, 74605-070
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Piracicaba, São Paulo, 13419-155
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Porto Alegre, Rio Grande do Sul, 90020-090
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Porto Alegre, Rio Grande do Sul, 90430-090
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Rio de Janeiro, Rio de Janeiro, 20230-130
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Salvador, Estado de Bahia, 41950-610
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São Paulo, São Paulo, 01246-000
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São Paulo, São Paulo, 01308-050
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São Paulo, São Paulo, 01317-000
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São Paulo, São Paulo, 01509-010
Israel12 sites
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Afula, 18101
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Beersheba, 8410101
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Haifa, 31096
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Haifa, 34362
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Holon, 58100
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Jerusalem, 91120-01
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Jerusalem, 9372212
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Kfar Saba, 44281
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Petah Tikva, 49100
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Ramat Gan, 52621
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Rehovot, 7610001
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Tel Aviv, 64239-06
Austria9 sites
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Graz, 8020
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Graz, 8036
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Innsbruck, 6020
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Ried-innkreis, 4910
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Salzburg, 5020
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Steyr, 4400
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Vienna, 1090
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Vienna, 1130
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Villach, 9500
Greece7 sites
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Athens, 115 28
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Athens, 11527
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Athens, 145 64
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Heraklion, Crete, 71110
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Larissa, 41 110
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Pátrai, 265 00
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Thessaloniki, 56429
India7 sites
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Bangalore, 560017
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Bangalore, 560054
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Hyderabad, 650034
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Jaipur, 302013
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Kochi, 682304
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New Delhi, 110029
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Pune, 411004
Russia6 sites
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Barnaul, 656049
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Moscow, 115478
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Obninsk, Kaluzhskaya Region, 249034
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Saint Petersburg, 197022
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Stavropol, 355045
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Ufa, 450054
Sweden6 sites
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Eskilstuna, 63188
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Falun, 79182
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Karlstad, 65185
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Örebro, 701 85
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Umeå
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Uppsala, 75185
Switzerland6 sites
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Aarau, 5001
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Baden, 5405
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Bellinzona, 6500
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Bern, 3010
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Geneva, 1211
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Zurich, 8091
Argentina5 sites
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Buenos Aires, C1199ACI
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Buenos Aires, C1280AEB
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Buenos Aires, C1426ANZ
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Rosario, S2002KDS
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San Miguel de Tucumán, T4000IAK
Canada5 sites
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Calgary, Alberta, T2N 4N2
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Montreal, Quebec, H2L 4M1
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Ottawa, Ontario, K1H 8L6
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Québec, Quebec, G1R 3S1
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Toronto, Ontario, M5G 2M9
Hungary5 sites
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Budapest, 1122
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Budapest, 1125
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Debrecen, 4032
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Pécs, 7624
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Szeged, 6720
Turkey (Türkiye)4 sites
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Ankara, 06230
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Ankara, 06500
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Diyarbakır, 10000
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Istanbul, 34390
Bulgaria3 sites
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Sofia, 1756
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Varna, 9010
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Veliko Tarnovo, 5000
Denmark3 sites
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Aalborg, 9000
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Roskilde, 4000
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Vejle, 7100
Estonia3 sites
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Tallinn, 11312
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Tallinn, 13419
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Tartu, 50406
Latvia3 sites
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Daugavpils, 5417
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Riga, LV 1079
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Riga, LV-1002
Lithuania3 sites
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Kaunas, 50009
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Klaipėda, 92288
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Vilnius, 08660
Mexico3 sites
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Distrito Federal, 14080
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Oaxaca City, 68000
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Toluca, 50180
Romania3 sites
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Bucharest, 022328
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Cluj-Napoca, 400015
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Iași, 700106
South Africa3 sites
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Durban, 4058
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Johannesburg, 2193
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Sandton, 2196
Taiwan3 sites
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Taipei, 110
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Taipei, 112
Study site
Taoyuan Hsien, 333
About this study
Official title: 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.
- Conditions
- Ovarian Cancer
- Being tested
- Paclitaxel, Bevacizumab, Carboplatin
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
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
BevacizumabDrug
Also called Avastin
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
CarboplatinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Paclitaxel + Carboplatin | Experimental | 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). Receives: Drug: Paclitaxel; Drug: Bevacizumab; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,021 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01239732
- Sponsor's protocol ID
- MO22923
- Other IDs
- 2010-019525-34
- Status last verified
- May 2016
- First submitted
- 10 Nov 2010
- Last updated
- 10 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 27749456