Conditions: Breast Cancer
Keywords: endocrine therapy bevacizumab breast cancer first-line therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 380
Healthy volunteers: no

Brief summary:
Locally advanced or metastatic breast cancer in postmenopausal women with negative Human Epidermal Growth Factor Receptor 2 (HER2), who are candidates for hormone treatment and who have not received previous chemotherapy or hormonotherapy for the metastatic disease.

Detailed description:
The main endpoint of the study is progression-free survival (PFS). It has been calculated that 378 patients will need to be included, according to the following assumptions:

* Recruitment period of 21 months.
* Minimum follow-up period of 9 months.
* PFS of 9 months in the control arm (letrozole in monotherapy). Using a two-sided log-rank test, for a 5% α level, 344 patients (172 in each treatment arm) will be required for 270 events to occur, which will provide an 80% power for detecting a hazard ratio of 0.69 (corresponding to a PFS median of 13 months in the bevacizumab arm). This sample size has been adjusted for an intermediate analysis when 2/3 of the total of required events have occurred. This intermediate analysis can be avoided if, at the time in which it must be carried out, it is estimated that the final analysis will be carried out in 4 months.

Taking into account a 10% percentage of losses, 378 patients are expected to be included in the study.

An intermediate safety evaluation will be carried out when 63 patients have finished their treatment in each treatment arm.

A multicenter, randomized phase III clinical trial. After verifying the selection criteria, the patients will be randomized to receive letrozole alone or in combination with bevacizumab. Before randomization, the patients will be stratified according to the following prognosis factors:

* Estrogen Receptor (ER)+ / Progesterone Receptor (PgR)+ vs the other options (ER+/PgR- vs ER-/PgR+)
* Previous adjuvant hormonotherapy (yes/no)
* Status: locally advanced vs metastatic.
* Measurable vs non measurable disease
* Visceral disease (yes/no)
* PFS.

Arms:
arm 1: Endocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent. arm 2: Endocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg i.v. on day 1 every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.

Interventions: intervention 1: Letrozole intervention 2: Bevacizumab intervention 3: Fulvestrant
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document: