A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Breast Cancer Progressing After First-Line Therapy With Avastin and Chemotherapy (TANIA)

• ClinicalTrials.gov Identifier: NCT01250379
• Recruitment Status: Completed
• First Posted: November 30, 2010
• Results First Posted: June 30, 2015
• Last Update Posted: February 11, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: bevacizumab [Avastin]; Drug: Chemotherapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 494 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Study Evaluating the Efficacy and Safety of Continued and Re-induced Bevacizumab in Combination With Chemotherapy for Patients With Locally Recurrent or Metastatic Breast Cancer After First-line Chemotherapy and Bevacizumab Treatment
• Study Start Date: February 2011
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1	Drug: Chemotherapy; Standard chemotherapy (doublets not allowed)
Experimental: 2	Drug: bevacizumab [Avastin]; 10 mg/ kg iv every 2 weeks or 15 mg/kg iv every 3 weeks; Drug: Chemotherapy; Standard chemotherapy (doublets not allowed)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Second-Line Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: 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 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.
2. Second-Line PFS [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years ]
   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.
3. Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 6 [ Time Frame: 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.
4. Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 12 [ Time Frame: 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.
5. Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 18 [ Time Frame: 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.
6. Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 24 [ Time Frame: 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.

Secondary Outcome Measures :

1. Second-Line PFS by Baseline Risk Factor (Data Cutoff 20 December 2013) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years ]
   The median time, in months, from randomization to second-line PFS event according to the following baseline risk factors: hormone receptor negative, HER2 negative (triple negative), hormone receptor positive/HER-2 negative (HR-pos/HER-neg), first-line PFS less than (<) 6 months, first-line PFS greater than or equal to (≥) 6 months, taxane chemotherapy (chemo), non-taxane chemo, vinorelbine chemo, LDH ≤ 1.5 upper limit of normal (ULN), LDH greater than (>) 1.5 ULN, < 65 years of age, ≥ 65 years of age, < 70 years of age, ≥ 70 years of age, < 3 metastatic organ sites, ≥ 3 metastatic organ sites, bevacizumab-free (B-free) interval ≤ 6 weeks, B-free > 6 weeks, disease-free (D-free) interval ≤ 24 months, D-free > 24 months, D-free ≤ 12 months, and D-free > 12 months. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented. PD: defined in Outcome measure 1. The 95% CI was estimated using Kaplan-Meier methodology.
2. 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) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years ]
   BOR was defined as a confirmed CR or PR during second-line treatment. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% Cl was determined using the Pearson-Clopper method.
3. Percentage of Participants With a Second-Line CR, PR, Stable Disease, and PD According to RECIST v1.1 (Data Cutoff 20 December 2013) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years ]
   For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; stable disease was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI was determined using the Pearson-Clopper method.
4. Duration of Second-Line Objective Response (Data Cutoff 20 December 2013) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years ]
   The median time, in months, from the date of the first second-line documentation of CR or PR according to RECIST v1.1 to the date of the first second-line documentation of PD or death due to any cause. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants with CR or PR who had experienced neither disease progression nor died were censored at the date of the last available tumor assessment when the participant was known to be progression free.
5. 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) [ Time Frame: Months 3, 6, and 9 ]
   Duration of objective response was defined as the median time, in months, from the date of the first second-line documentation of CR or PR to the date of the first second-line documentation of PD or death due to any cause. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants with CR or PR who had experienced neither disease progression nor died were censored at the date of the last available tumor assessment when the participant was known to be progression free.
6. Percentage of Participants With Third-Line PFS According to RECIST v1.1 [ Time Frame: First dose of third-line treatment until PD or death due to any cause (assessed every 8-9 weeks, over a period of approximately 14 months) ]
   Third-line PFS was defined as the time from the date of first dose of third-line bevacizumab and/or chemotherapy to the date of third-line PD or death due to any cause. 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. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
7. Third-Line PFS [ Time Frame: First dose of third-line treatment until PD or death due to any cause (over a period of approximately 14 months) ]
   The median time, in months, from the first dose of third-line bevacizumab and/or chemotherapy to third-line PD or death due to any cause. 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 third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
8. Percentage of Participants With Second- and Third-Line PFS According to RECIST v1.1 [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years ]
   Second- and third-line PFS was defined as the time from the date randomization to the date of third-line PD or death due to any cause. 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 third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
9. Second- and Third-Line PFS [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years ]
   The median time, in months, from randomization to second-line and third-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 third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
10. Percentage of Participants With Second- and Third-Line Tumor Progression [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years ]
    Second- and third-line tumor progression was defined as occurrence of third-line PD according to RECIST v1.1 or death due to progression of disease. 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 third-line PD or death due to progression of disease were censored at the date of last tumor assessment where non-progression was documented.
11. Time to Second- and Third-Line Tumor Progression [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years ]
    The median time, in months, from randomization to second- and third-line tumor progression. Second- and third-line tumor progression was defined as third-line PD according to RECIST v1.1 or death due to progression of disease. 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 third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
12. Percentage of Participants Who Died [ Time Frame: Baseline until death (up to approximately 4 years) ]
    Percentage of participants who died due to any reason were reported.
13. Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 4 years) ]
    OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Participants who had not died were censored at the date the patient was last known to be alive.
14. Percentage of Participants Estimated to be Surviving at Months 6, 12, 18, and 24 [ Time Frame: Months 6, 12, 18, and 24 ]
    OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause.
15. Percentage of Participants Experiencing Problems by European Quality of Life Instrument (EQ-5D) Category (Data Cutoff 20 December 2013) [ Time Frame: Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years) ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility (M) ("no problems"="I have no problems in walking about" to "extreme problems"="I am confined to bed"), self-care (SC) ("no problems"="I have no problems with self-care" to "extreme problems"="I am unable to wash or dress myself"), usual activities (UA) ("no problems"="I have no problems performing my usual activities" to "extreme problems"="I am unable to perform my usual activities"), pain/discomfort (P/D) ("no problems"="I have no pain or discomfort" to "extreme problems"="I have extreme pain or discomfort"), and anxiety/depression (A/D) ("no problems"="I am not anxious or depressed" to "extreme problems"='I am extremely anxious or depressed").
16. Quality of Life Assessed As an Index Score Using the EQ-5D (Data Cutoff 20 December 2013) [ Time Frame: Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years) ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on large population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D index score ranging from -0.59 (extreme problems) to +1 (no problems).
17. Change From Baseline in EQ-5D Index Scores (Data Cutoff 20 December 2013) [ Time Frame: Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years) ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on large population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D index score ranging from -0.59 (extreme problems) to +1 (no problems) where a negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life.
18. Quality of Life Assessed Using the EQ-5D Visual Analogue Scale (VAS) Scores (Data Cutoff 20 December 2013) [ Time Frame: Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years) ]
    The participant was asked to rate their overall health on a 0-100 millimeter (mm) vertical scale, where the lowest endpoint=0 (labeled as worst imaginable health state) and the highest endpoint =100 (labeled as the best imaginable health state). The participant marked the line corresponding to their assessment and the distance from the bottom was measured in millimeters. A higher value indicated a better health state.
19. Change From Baseline in VAS Scores (Data Cutoff 20 December 2013) [ Time Frame: Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years) ]
    The participant was asked to rate their overall health on a 0-100 mm vertical scale, where the lowest endpoint = 0 (labeled as worst imaginable health state) and the highest endpoint =100 (labeled as the best imaginable health state). The participant marked the line corresponding to their assessment and the distance from the bottom was measured in millimeters. A negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life.
20. Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores (Data Cutoff 20 December 2013) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years) ]
    The Functional Assessment of Cancer Therapy-Breast (FACT-B) is composed of 5 multi-item sections where participants responded to questions assessing symptoms (scale: 0-4; 0="not at all" and 4="very much"), as follows: physical well-being (PWB) (7 items, total score 0-28), social/family well-being (SWB) (7 items, total score 0-28), emotional well-being (EWB) (6 items, total score 0-24), functional well-being (FWB) (7 items, total score 0-28); and breast cancer score based on the additional concerns section of FACT-B (10 items, total score 0-40). The FACT-B Trial Outcomes Index (TOI) score=sum of PWB, FWB, and breast cancer score subscale scores (total score 0-96). The Functional Assessment of Cancer Therapy-General (FACT-G) total score=sum of PWB, SWB, EWB, and FWB subscales scores (total score 0-108). The FACT-B total score=sum of PWB, SWB, EWB, FWB, and breast cancer score subscales scores (total score 0-148). In all cases a higher value indicated a better perceived quality of life.
21. Change From Baseline in FACT-B Scores (Data Cutoff 20 December 2013) [ Time Frame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years) ]
    The FACT-B is composed of 5 multi-item sections where participants responded to questions assessing symptoms (scale: 0-4; 0="not at all" and 4="very much"), as follows: PWB (7 items, total score 0-28), SWB (7 items, total score 0-28), EWB (6 items, total score 0-24), FWB (7 items, total score 0-28); and breast cancer score based on the additional concerns section of FACT-B (10 items, total score 0-40). The FACT-B TOI score=sum of PWB, FWB, and breast cancer score subscale scores (total score 0-96). The FACT-G total score=sum of PWB, SWB, EWB, and FWB subscales scores (total score 0-108). The FACT-B total score=sum of PWB, SWB, EWB, FWB, and breast cancer score subscale scores (total score 0-148). In all cases a higher value indicated a better perceived quality of life.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

Argentina

Buenos Aires, Argentina, C1199ACI

Buenos Aires, Argentina, C1280AEB

Buenos Aires, Argentina, C1426ANZ

San Miguel de Tucuman, Argentina, T4000IAK

Austria

Feldkirch, Austria, 6807

Graz, Austria, 8036

Innsbruck, Austria, 6020

Krems, Austria, 3500

Salzburg, Austria, 5020

Steyr, Austria, 4400

Villach, Austria, 9500

Wien, Austria, 1090

Brazil

Goiania, GO, Brazil, 74140-050

Porto Alegre, RS, Brazil, 90430-090

Itajai, SC, Brazil, 88301-220

Croatia

Split, Croatia, 21000

France

Amiens, France, 80090

Angers, France, 49933

Besancon, France, 25030

Bordeaux, France, 33000

Boulogne Sur Mer, France, 62222

Brest, France, 29609

Caen, France, 14076

Clermont Ferrand, France, 63011

Dijon, France, 21079

Grenoble, France, 38028

Limoges, France, 87039

Marseille, France, 13285

Montpellier, France, 34298

Nancy, France, 54100

Nantes, France, 44202

Paris, France, 75970

Pierre Benite, France, 69495

Reims CEDEX, France, 51056

Rouen, France, 76038

Saint Gregoire, France, 35768

Saint Jean, France, 31240

St Cloud, France, 92210

St Priest En Jarez, France, 42271

St Quentin, France, 02321

Strasbourg, France, 67010

Toulouse, France, 31076

Germany

Amberg, Germany, 92224

Aschaffenburg, Germany, 63739

Berlin, Germany, 10367

Berlin, Germany, 10719

Bielefeld, Germany, 33604

Chemnitz, Germany, 09116

Dresden, Germany, 01307

Düsseldorf, Germany, 40235

Essen, Germany, 45122

Essen, Germany, 45136

Freiburg, Germany, 79110

Göttingen, Germany, 37073

Hamburg, Germany, 20249

Hannover, Germany, 30177

Heidelberg, Germany, 69115

Heidelberg, Germany, 69120

Karlsruhe, Germany, 76135

Koeln, Germany, 50935

Mannheim, Germany, 68161

Muenster, Germany, 48149

München, Germany, 80639

Naunhof, Germany, 04683

Neuss, Germany, 41462

Nordhausen, Germany, 99734

Osnabrueck, Germany, 49076

Ravensburg, Germany, 88212

Stade, Germany, 21680

Stralsund, Germany, 18435

Wiesbaden, Germany, 65199

Greece

Athens, Greece, 11528

Ioannina, Greece, 455 00

Patras, Greece, 265 00

Thessaloniki, Greece, 546 45

Hungary

Budapest, Hungary, 1122

Budapest, Hungary, 1145

Szeged, Hungary, 6720

Israel

Beer Sheva, Israel, 8410101

Jerusalem, Israel, 91120

Kfar-Saba, Israel, 4428164

Petach Tikva, Israel, 4941492

Ramat Gan, Israel, 52620-00

Rehovot, Israel, 7610001

Tel Aviv, Israel, 6423906

Tel Aviv, Israel

Italy

Cosenza, Calabria, Italy, 87100

Benevento, Campania, Italy, 82100

Napoli, Campania, Italy, 80131

Reggio Emilia, Emilia-Romagna, Italy, 42100

Udine, Friuli-Venezia Giulia, Italy, 33100

Roma, Lazio, Italy, 00168

Monza, Lombardia, Italy, 20052

Macerata, Marche, Italy, 62100

Cagliari, Sardegna, Italy, 09121

Sassari, Sardegna, Italy, 07100

Catania, Sicilia, Italy, 95100

Firenze, Toscana, Italy, 50134

Pisa, Toscana, Italy, 56100

Pontedera, Toscana, Italy, 56025

Verona, Veneto, Italy, 37126

Slovakia

Bardejov, Slovakia, 085 01

Bratislava, Slovakia, 812 50

Kosice, Slovakia, 04001

Nove Zamky, Slovakia, 940 34

Presov, Slovakia, 080 01

Spain

Santander, Cantabria, Spain, 39008

San Sebastian, Guipuzcoa, Spain, 20080

Palma De Mallorca, Islas Baleares, Spain, 07014

La Laguna, Tenerife, Spain, 38320

Barcelona, Spain, 08035

Barcelona, Spain, 08036

Barcelona, Spain, 08041

Castellon, Spain, 12002

Cordoba, Spain, 14004

Leon, Spain, 24071

Lerida, Spain, 25198

Madrid, Spain, 28007

Madrid, Spain, 28033

Madrid, Spain, 28034

Madrid, Spain, 28040

Madrid, Spain, 28041

Madrid, Spain, 28046

Madrid, Spain, 28223

Malaga, Spain, 29010

Murcia, Spain, 30008

Sevilla, Spain, 41014

Valencia, Spain, 46009

Zaragoza, Spain, 50009

Switzerland

Aarau, Switzerland, 5000

Chur, Switzerland, 7000

Zürich, Switzerland, 8038

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01250379
• Other Study ID Numbers: MO22998; 2010-020998-16
• First Posted: November 30, 2010
• Results First Posted: June 30, 2015
• Last Update Posted: February 11, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors