NCT01250379

Brief Summary

This randomized, open-label, parallel-group study will assess the efficacy and s afety of Avastin (bevacizumab) in combination with chemotherapy versus chemother apy alone as second- and third-line therapy in patients with locally recurrent o r metastatic breast cancer progressing after first-line therapy with Avastin and chemotherapy. Patients will be randomized to receive either Avastin (15 mg/kg e very 3 weeks or 10 mg/kg every 2 weeks intravenously) plus standard chemotherapy or chemotherapy alone. Anticipated time on study treatment is until third-line disease progression or unacceptable toxicity occurs.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
494

participants targeted

Target at P50-P75 for phase_3 breast-cancer

Timeline
Completed

Started Feb 2011

Geographic Reach
13 countries

132 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 25, 2010

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 30, 2010

Completed
2 months until next milestone

Study Start

First participant enrolled

February 1, 2011

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
4 months until next milestone

Results Posted

Study results publicly available

June 30, 2015

Completed
Last Updated

February 11, 2016

Status Verified

January 1, 2016

Enrollment Period

2.8 years

First QC Date

November 25, 2010

Results QC Date

June 5, 2015

Last Update Submit

January 12, 2016

Conditions

Outcome Measures

Primary Outcomes (6)

  • Percentage of Participants With Second-Line Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)

    Second-line PFS was defined as the time from randomization to progressive disease (PD) or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For target lesions (TLs), PD was defined at least a 20 percent (%) increase in the sum of the largest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For non-target lesions (NTLs), PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Baseline (less than or equal to [≤] 28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Second-Line PFS

    The median time, in months, from randomization to second-line PFS event. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 6

    Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Month 6

  • Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 12

    Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without secondline PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Month 12

  • Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 18

    Second-line PFS was defined as the time from randomization to PD or death due to any cause during their secondline of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Month 18

  • Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 24

    Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.

    Month 24

Secondary Outcomes (21)

  • Second-Line PFS by Baseline Risk Factor (Data Cutoff 20 December 2013)

    Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Percentage of Participants With a Second-Line Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 (Data Cutoff 20 December 2013)

    Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Percentage of Participants With a Second-Line CR, PR, Stable Disease, and PD According to RECIST v1.1 (Data Cutoff 20 December 2013)

    Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Duration of Second-Line Objective Response (Data Cutoff 20 December 2013)

    Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years

  • Percentage of Participants With a Second-Line Documented CR or PR According to RECIST v1.1 Estimated to be Alive and Free of Disease Progression at Months 3, 6, and 9 (Data Cutoff 20 December 2013)

    Months 3, 6, and 9

  • +16 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR
Drug: Chemotherapy

2

EXPERIMENTAL
Drug: bevacizumab [Avastin]Drug: Chemotherapy

Interventions

10 mg/ kg iv every 2 weeks or 15 mg/kg iv every 3 weeks

2

Standard chemotherapy (doublets not allowed)

12

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female patients, \>/= 18 years of age
  • Histologically confirmed HER2-negative breast cancer
  • Disease progression during or following first-line treatment with Avastin and chemotherapy for locally recurrent or metastatic breast cancer
  • Avastin treatment in first-line setting must have been a minimum of 4 cycles (15 mg/kg) or 6 cycles (10 mg/kg) in combination with chemotherapy
  • ECOG performance status 0-2
  • At least 28 days since prior radiation therapy or surgery and recovery from treatment

You may not qualify if:

  • Anti-angiogenic therapy or anti-vascular endothelial growth factors other than Avastin for first-line treatment
  • Active malignancy other than superficial basal cell and superficial squamous cell carcinoma of the skin, or in situ carcinoma of the cervix or breast within the last 5 years
  • Inadequate renal function
  • Clinically relevant cardio-vascular disease
  • Known CNS disease except for treated brain metastases
  • Chronic daily treatment with high-dose aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day)
  • Pregnant or lactating women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (132)

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Buenos Aires, C1199ACI, Argentina

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Buenos Aires, C1280AEB, Argentina

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Buenos Aires, C1426ANZ, Argentina

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San Miguel de Tucumán, T4000IAK, Argentina

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Feldkirch, 6807, Austria

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Krems, 3500, Austria

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Salzburg, 5020, Austria

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Steyr, 4400, Austria

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Vienna, 1090, Austria

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Villach, 9500, Austria

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Goiânia, Goiás, 74140-050, Brazil

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Porto Alegre, Rio Grande do Sul, 90430-090, Brazil

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Itajaí, Santa Catarina, 88301-220, Brazil

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Split, 21000, Croatia

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Amiens, 80090, France

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Angers, 49933, France

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Besançon, 25030, France

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Bordeaux, 33000, France

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Boulogne-sur-Mer, 62222, France

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Brest, 29609, France

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Caen, 14076, France

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Clermont-Ferrand, 63011, France

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Dijon, 21079, France

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Grenoble, 38028, France

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Limoges, 87039, France

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Marseille, 13285, France

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Montpellier, 34298, France

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Nancy, 54100, France

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Nantes, 44202, France

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Paris, 75970, France

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Pierre-Bénite, 69495, France

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Reims, 51056, France

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Rouen, 76038, France

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Saint-Cloud, 92210, France

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Saint-Grégoire, 35768, France

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Saint-Jean, 31240, France

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Saint-Priest-en-Jarez, 42271, France

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Saint-Quentin, 02321, France

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Strasbourg, 67010, France

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Toulouse, 31076, France

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Amberg, 92224, Germany

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Aschaffenburg, 63739, Germany

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Berlin, 10367, Germany

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Berlin, 10719, Germany

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Bielefeld, 33604, Germany

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Chemnitz, 09116, Germany

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Cologne, 50935, Germany

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Dresden, 01307, Germany

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Düsseldorf, 40235, Germany

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Essen, 45122, Germany

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Essen, 45136, Germany

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Freiburg im Breisgau, 79110, Germany

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Göttingen, 37073, Germany

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Hamburg, 20249, Germany

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Hanover, 30177, Germany

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Heidelberg, 69115, Germany

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Heidelberg, 69120, Germany

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Karlsruhe, 76135, Germany

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Mannheim, 68161, Germany

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München, 80639, Germany

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Münster, 48149, Germany

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Naunhof, 04683, Germany

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Neuss, 41462, Germany

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Nordhausen, 99734, Germany

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Osnabrück, 49076, Germany

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Ravensburg, 88212, Germany

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Stade, 21680, Germany

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Stralsund, 18435, Germany

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Wiesbaden, 65199, Germany

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Athens, 11528, Greece

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Ioannina, 455 00, Greece

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Pátrai, 265 00, Greece

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Thessaloniki, 546 45, Greece

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Budapest, 1122, Hungary

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Budapest, 1145, Hungary

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Szeged, 6720, Hungary

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Beersheba, 8410101, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 4941492, Israel

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Ramat Gan, 52620-00, Israel

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Rehovot, 7610001, Israel

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Tel Aviv, 6423906, Israel

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Tel Aviv, Israel

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Cosenza, Calabria, 87100, Italy

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Benevento, Campania, 82100, Italy

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Napoli, Campania, 80131, Italy

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Reggio Emilia, Emilia-Romagna, 42100, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Rome, Lazio, 00168, Italy

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Monza, Lombardy, 20052, Italy

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Cagliari, Sardinia, 09121, Italy

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Sassari, Sardinia, 07100, Italy

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Catania, Sicily, 95100, Italy

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Macerata, The Marches, 62100, Italy

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Florence, Tuscany, 50134, Italy

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Pisa, Tuscany, 56100, Italy

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Pontedera, Tuscany, 56025, Italy

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Verona, Veneto, 37126, Italy

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Bardejov, 085 01, Slovakia

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Bratislava, 812 50, Slovakia

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Košice, 04001, Slovakia

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Nové Zámky, 940 34, Slovakia

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Prešov, 080 01, Slovakia

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Palma de Mallorca, Balearic Islands, 07014, Spain

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08036, Spain

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Barcelona, Barcelona, 08041, Spain

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Santander, Cantabria, 39008, Spain

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Castellon, Castellon, 12002, Spain

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Córdoba, Cordoba, 14004, Spain

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Donostia / San Sebastian, Guipuzcoa, 20080, Spain

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León, Leon, 24071, Spain

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Lleida, Lerida, 25198, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28033, Spain

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Madrid, Madrid, 28034, Spain

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Madrid, Madrid, 28040, Spain

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Madrid, Madrid, 28041, Spain

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Madrid, Madrid, 28046, Spain

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Madrid, Madrid, 28223, Spain

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Málaga, Malaga, 29010, Spain

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Murcia, Murcia, 30008, Spain

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Seville, Sevilla, 41014, Spain

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San Cristóbal de La Laguna, Tenerife, 38320, Spain

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Valencia, Valencia, 46009, Spain

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Zaragoza, Zaragoza, 50009, Spain

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Aarau, 5000, Switzerland

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Chur, 7000, Switzerland

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Zurich, 8038, Switzerland

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Related Publications (2)

  • Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Levy C, Brain E, Pivot X, Putzu C, Gonzalez Martin A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. doi: 10.1093/annonc/mdw316. Epub 2016 Aug 8.

  • von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. doi: 10.1016/S1470-2045(14)70439-5. Epub 2014 Sep 28.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

BevacizumabDrug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsTherapeutics

Results Point of Contact

Title
Medical Communications
Organization
Hoffman-LaRoche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 25, 2010

First Posted

November 30, 2010

Study Start

February 1, 2011

Primary Completion

December 1, 2013

Study Completion

March 1, 2015

Last Updated

February 11, 2016

Results First Posted

June 30, 2015

Record last verified: 2016-01

Locations