Clinical trial NCT00391092: A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2 Positive Metastatic Breast Cancer.
Official title: A Randomized, Open-label Study to Compare the Effect of First-line Treatment With Avastin in Combination With Herceptin/Docetaxel and Herceptin/Docetaxel Alone on Progression-free Survival in Patients With HER2 Positive Locally Recurrent or Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2006-10-23
Enrollment: 424
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 arm study will compare the efficacy and safety of Avastin plus Herceptin/docetaxel, versus Herceptin/docetaxel alone, in patients with HER2 positive locally recurrent or metastatic breast cancer who have not received prior chemotherapy for their metastatic disease. Patients will be randomized 1:1 to receive either Avastin (15mg/kg iv q3weeks) + Herceptin (8mg/kg iv loading dose and 6mg/kg iv q3weeks maintenance) + docetaxel (100mg/m2 iv q3weeks) or Herceptin + docetaxel alone. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>=18 years of age;
* HER2 positive breast cancer with locally recurrent or metastatic lesions;
* eligible for chemotherapy;
* baseline LVEF \>=50%.

Exclusion Criteria:

* previous chemotherapy for metastatic or locally recurrent breast cancer;
* previous radiotherapy for metastatic breast cancer (except for metastatic bone pain relief);
* other primary tumor within last 5 years, with the exception of basal or squamous skin cancer, or in situ cancer of the cervix;
* clinically significant cardiovascular disease;
* chronic daily treatment with aspirin (\>325mg/day) or clopidogrel (\>75mg/day).

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
measure: Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR) in Participants With Measurable Disease at Baseline
timeFrame: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
measure: Duration of Response (DR)
timeFrame: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
measure: Time to Treatment Failure (TTF)
timeFrame: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
measure: Functional Assessment of Cancer Therapy - Generic (FACT-G) and Functional Assessment of Cancer Therapy - Breast (FACT-B) Subscale Scores
timeFrame: Baseline, Cycles 3, 5, 11, and post progressive disease (PD; 14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])
measure: Change From Baseline for FACT-G and FACT-B
timeFrame: Baseline, Cycles 3, 5, 11, and post PD (14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Mar del Plata
country: Argentina
city: Mendoza
country: Argentina
city: Salta
country: Argentina
city: San Martin
country: Argentina
city: Santa Fe
country: Argentina
city: Santa Fe
country: Argentina
city: Lismore
country: Australia
state: New South Wales
city: Newcastle
country: Australia
state: New South Wales
city: Port Macquarie
country: Australia
state: New South Wales
city: Wahroonga
country: Australia
state: New South Wales
city: Wollongong
country: Australia
state: New South Wales
city: Auchenflower
country: Australia
state: Queensland
city: Nambour
country: Australia
state: Queensland
city: Fitzroy
country: Australia
state: Victoria
city: Geelong
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Graz
country: Austria
city: Salzburg
country: Austria
city: Vöcklabruck
country: Austria
city: Wien
country: Austria
city: Banja Luka
country: Bosnia and Herzegovina
city: Sarajevo
country: Bosnia and Herzegovina
city: Tuzla
country: Bosnia and Herzegovina
city: Goiania
country: Brazil
state: GO
city: Porto Alegre
country: Brazil
state: RS
city: Florianopolis
country: Brazil
state: SC
city: Barretos
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
city: Quebec
country: Canada
city: Praha 2
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Avignon
country: France
city: Besancon
country: France
city: Bordeaux
country: France
city: Caen
country: France
city: Clermont Ferrand
country: France
city: Dijon
country: France
city: Lille
country: France
city: Montpellier
country: France
city: Villejuif
country: France
city: Parma
country: Italy
state: Emilia-Romagna
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Acapulco
country: Mexico
city: Guadalajara
country: Mexico
city: Merida
country: Mexico
city: Monterrey
country: Mexico
city: Torreon
country: Mexico
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj Napoca
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: UFA
country: Russian Federation
city: Sabadell, Barcelona
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Zaragoza
country: Spain
city: Izmir
country: Turkey
city: Sıhhiye, ANKARA
country: Turkey
city: Exeter
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Preston
country: United Kingdom
city: Rhyl
country: United Kingdom
city: Stoke-on-Trent
country: United Kingdom
city: Weston Super Mare
country: United Kingdom
city: Montevideo
country: Uruguay
city: Montevideo
country: Uruguay
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. doi: 10.1200/JCO.2012.44.7912. Epub 2013 Apr 8.