Clinical trial NCT01250379: A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Breast Cancer Progressing After First-Line Therapy With Avastin and Chemotherapy (TANIA)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-11-30
Enrollment: 494
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Second-Line Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
timeFrame: 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
measure: Second-Line PFS
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
measure: Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 6
timeFrame: Month 6
measure: Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 12
timeFrame: Month 12
measure: Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 18
timeFrame: Month 18
measure: Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 24
timeFrame: Month 24
Secondary outcomes:
measure: Second-Line PFS by Baseline Risk Factor (Data Cutoff 20 December 2013)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
measure: 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)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
measure: Percentage of Participants With a Second-Line CR, PR, Stable Disease, and PD According to RECIST v1.1 (Data Cutoff 20 December 2013)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
measure: Duration of Second-Line Objective Response (Data Cutoff 20 December 2013)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
measure: 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)
timeFrame: Months 3, 6, and 9
measure: Percentage of Participants With Third-Line PFS According to RECIST v1.1
timeFrame: 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)
measure: Third-Line PFS
timeFrame: First dose of third-line treatment until PD or death due to any cause (over a period of approximately 14 months)
measure: Percentage of Participants With Second- and Third-Line PFS According to RECIST v1.1
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years
measure: Second- and Third-Line PFS
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years
measure: Percentage of Participants With Second- and Third-Line Tumor Progression
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years
measure: Time to Second- and Third-Line Tumor Progression
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years
measure: Percentage of Participants Who Died
timeFrame: Baseline until death (up to approximately 4 years)
measure: Overall Survival (OS)
timeFrame: Baseline until death (up to approximately 4 years)
measure: Percentage of Participants Estimated to be Surviving at Months 6, 12, 18, and 24
timeFrame: Months 6, 12, 18, and 24
measure: Percentage of Participants Experiencing Problems by European Quality of Life Instrument (EQ-5D) Category (Data Cutoff 20 December 2013)
timeFrame: 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)
measure: Quality of Life Assessed As an Index Score Using the EQ-5D (Data Cutoff 20 December 2013)
timeFrame: 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)
measure: Change From Baseline in EQ-5D Index Scores (Data Cutoff 20 December 2013)
timeFrame: 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)
measure: Quality of Life Assessed Using the EQ-5D Visual Analogue Scale (VAS) Scores (Data Cutoff 20 December 2013)
timeFrame: 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)
measure: Change From Baseline in VAS Scores (Data Cutoff 20 December 2013)
timeFrame: 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)
measure: Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores (Data Cutoff 20 December 2013)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years)
measure: Change From Baseline in FACT-B Scores (Data Cutoff 20 December 2013)
timeFrame: Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: San Miguel de Tucuman
country: Argentina
city: Feldkirch
country: Austria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Krems
country: Austria
city: Salzburg
country: Austria
city: Steyr
country: Austria
city: Villach
country: Austria
city: Wien
country: Austria
city: Goiania
country: Brazil
state: GO
city: Porto Alegre
country: Brazil
state: RS
city: Itajai
country: Brazil
state: SC
city: Split
country: Croatia
city: Amiens
country: France
city: Angers
country: France
city: Besancon
country: France
city: Bordeaux
country: France
city: Boulogne Sur Mer
country: France
city: Brest
country: France
city: Caen
country: France
city: Clermont Ferrand
country: France
city: Dijon
country: France
city: Grenoble
country: France
city: Limoges
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nancy
country: France
city: Nantes
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Reims CEDEX
country: France
city: Rouen
country: France
city: Saint Gregoire
country: France
city: Saint Jean
country: France
city: St Cloud
country: France
city: St Priest En Jarez
country: France
city: St Quentin
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Amberg
country: Germany
city: Aschaffenburg
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Chemnitz
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Göttingen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Heidelberg
country: Germany
city: Karlsruhe
country: Germany
city: Koeln
country: Germany
city: Mannheim
country: Germany
city: Muenster
country: Germany
city: München
country: Germany
city: Naunhof
country: Germany
city: Neuss
country: Germany
city: Nordhausen
country: Germany
city: Osnabrueck
country: Germany
city: Ravensburg
country: Germany
city: Stade
country: Germany
city: Stralsund
country: Germany
city: Wiesbaden
country: Germany
city: Athens
country: Greece
city: Ioannina
country: Greece
city: Patras
country: Greece
city: Thessaloniki
country: Greece
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Szeged
country: Hungary
city: Beer Sheva
country: Israel
city: Jerusalem
country: Israel
city: Kfar-Saba
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Tel Aviv
country: Israel
city: Cosenza
country: Italy
state: Calabria
city: Benevento
country: Italy
state: Campania
city: Napoli
country: Italy
state: Campania
city: Reggio Emilia
country: Italy
state: Emilia-Romagna
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Monza
country: Italy
state: Lombardia
city: Macerata
country: Italy
state: Marche
city: Cagliari
country: Italy
state: Sardegna
city: Sassari
country: Italy
state: Sardegna
city: Catania
country: Italy
state: Sicilia
city: Firenze
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Pontedera
country: Italy
state: Toscana
city: Verona
country: Italy
state: Veneto
city: Bardejov
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice
country: Slovakia
city: Nove Zamky
country: Slovakia
city: Presov
country: Slovakia
city: Santander
country: Spain
state: Cantabria
city: San Sebastian
country: Spain
state: Guipuzcoa
city: Palma De Mallorca
country: Spain
state: Islas Baleares
city: La Laguna
country: Spain
state: Tenerife
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Castellon
country: Spain
city: Cordoba
country: Spain
city: Leon
country: Spain
city: Lerida
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Aarau
country: Switzerland
city: Chur
country: Switzerland
city: Zürich
country: Switzerland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.