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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01239732
First received: November 10, 2010
Last updated: May 3, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Ovarian Cancer
Drug: Paclitaxel
Drug: Bevacizumab
Drug: Carboplatin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With at Least One Adverse Event (AE) [ Time Frame: Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years) ] [ Designated as safety issue: No ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving an Overall Response by 50% Carcinoma Antigen 125 (CA-125) Response Criteria [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving an Overall Response by RECIST Version 1.0 and/or 50% CA-125 Response Criteria [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Duration of Objective Response (DOR) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Overall Survival (OS) [ Time Frame: First administration of any study treatment until death or data cutoff 07 December 2014, up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Biological Progression-free Interval [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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).


Enrollment: 1021
Study Start Date: December 2010
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239732

  Hide Study Locations
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, 1090
Wien, Austria, 1130
Brazil
Salvador, BA, Brazil, 41950-610
Fortaleza, CE, Brazil, 60125-120
Goiania, GO, Brazil, 74605-070
Curitiba, PR, Brazil, 80530-010
Rio de Janeiro, RJ, Brazil, 20230-130
Porto Alegre, RS, Brazil, 90020-090
Porto Alegre, RS, Brazil, 90430-090
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, Alberta
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H2L 4M1
Canada
Quebec, Canada, G1R 3S1
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, 75231
Paris, France, 75571
Paris, France, 75651
Paris, France, 75674
Paris, France, 75908
Paris, France, 75970
Reims CEDEX, France, 51056
Strasbourg, France, 67065
Toulouse, France, 31059
Villejuif, France, 94805
Greece
Athens, Greece, 115 28
Athens, Greece, 11527
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, 852
Hong Kong, Hong Kong
Hungary
Budapest, Hungary, 1122
Budapest, Hungary, 1125
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, 31096
Haifa, Israel, 34362
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
Napoli, Campania, Italy, 80131
Bologna, Emilia-Romagna, Italy, 40138
Meldola, Emilia-Romagna, Italy, 47014
Roma, Lazio, Italy, 00128
Roma, Lazio, Italy, 00157
Genova, Liguria, Italy, 16128
Brescia, Lombardia, Italy, 25123
Milano, Lombardia, Italy, 20141
Milano, Lombardia, Italy, 20162
Monza, Lombardia, Italy, 20052
Saronno, Lombardia, Italy, 21047
Novara, Piemonte, Italy, 28100
Torino, Piemonte, Italy, 10126
Torino, Piemonte, Italy, 10128
Palermo, Sicilia, Italy, 90146
Firenze, Toscana, Italy, 50139
Pisa, Toscana, Italy, 56126
Perugia, Umbria, Italy, 06123
Terni, Umbria, Italy, 05100
Kuwait
Shuwaikh, Kuwait, 70653
Latvia
Daugavpils, Latvia, 5417
Riga, Latvia, LV 1079
Riga, Latvia, LV-1002
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, 2512 VA
Den Haag, Netherlands, 2545 CH
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
Elda, Alicante, Spain, 03600
Oviedo, Asturias, Spain, 33011
Llerena (Badajoz), Badajoz, Spain, 06900
Manresa, Barcelona, Spain, 08243
Cádiz, Cadiz, Spain, 11009
Jerez de La Frontera, Cadiz, Spain, 11407
San Sebastian de Los Reyes, Guipuzcoa, Spain, 28702
San Sebastian, Guipuzcoa, Spain, 20080
Palma De Mallorca, Islas Baleares, Spain, 07014
Palma de Mallorca, Islas Baleares, Spain, 07198
Santiago de Compostela, La Coruña, Spain, 15706
Las Palmas de Gran Canaria, Las Palmas, Spain, 35020
Leganes, Madrid, Spain, 28911
Reus, Tarragona, Spain, 43204
La Laguna, Tenerife, Spain, 38320
Santa Cruz de Tenerife, Tenerife, Spain, 38010
San Juan, Valencia, Spain, 03550
Barakaldo, Vizcaya, Spain, 48903
Bilbao, Vizcaya, Spain, 48013
Albacete, Spain, 02006
Alicante, Spain, 3010
Badajoz, Spain, 06080
Barcelona, Spain, 08003
Barcelona, Spain, 08017
Barcelona, Spain, 08036
Barcelona, Spain, 08906
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, 28002
Madrid, Spain, 28007
Madrid, Spain, 28033
Madrid, Spain, 28040
Madrid, Spain, 28041
Madrid, Spain, 28050
Madrid, Spain, 28222
Malaga, Spain, 29010
Malaga, Spain, 29011
Navarra, Spain, 31008
Salamanca, Spain, 37007
Segovia, Spain, 40002
Sevilla, Spain, 41009
Sevilla, Spain, 41014
Toledo, Spain, 45004
Valencia, Spain, 46009
Valencia, Spain, 46015
Valencia, Spain, 46017
Valencia, Spain, 46026
Valladolid, Spain, 47010
Zaragoza, Spain, 50009
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, 06230
Ankara, Turkey, 06500
Diyarbakir, Turkey, 10000
Istanbul, Turkey, 34390
Uruguay
Montevideo, Uruguay, 11600
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01239732     History of Changes
Other Study ID Numbers: MO22923  2010-019525-34 
Study First Received: November 10, 2010
Results First Received: March 17, 2016
Last Updated: May 3, 2016
Health Authority: Serbia: Agency for Drugs and Medicinal Devices

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016