Clinical trial NCT00240071
Conditions: Metastatic Breast Cancer
Keywords: Breast cancer Metastatic breast cancer Hormonal therapy Bevacizumab
Sponsor: University of Alabama at Birmingham
Start date: 2005-10-01; Completion date: 2011-04-01
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine if acquired hormone therapy resistance can be reversed by Avastin (Bevacizumab), as measured by time to disease progression and evaluate toxicity of the combination of hormone treatment plus Avastin (Bevacizumab).

Detailed description:
This is a single institution, open-label study designed to evaluate safety and efficacy of Avastin (Bevacizumab) combined with an endocrine agent in patients with estrogen and/or progesterone receptor positive metastatic breast carcinoma who have acquired resistance to at least one hormonal agent. Patients will be treated with the same hormonal agent that was used previously assuming that the patient had a partial or complete response (for at least 6 months) followed by a clear disease progression using the Response Evaluation Criteria in solid Tumors (RECIST Criteria). Patients with stable disease for a prolonged time (for at least 6 months) will be also eligible to enter in the trial. Patients who have not had interval studies to evaluate disease response will be considered eligible if they have remained clinically stable (i.e. stable performance status (PS), no increasing pain) and on the same hormone for at least 6 months, and now they have signs and symptoms of clinical progression (i.e. elevated tumor markers, increasing bone pain, worsening performance status). Patients must have histologically confirmed measurable and/or evaluable metastatic breast cancer with positive estrogen and/or progesterone receptors. Patients can have up to an 8-12 week break in therapy (discontinuation of hormonal therapy) and still remain eligible for the study as long as the documentation of disease progression is determined before the 8-12 week break in hormonal therapy.

The type and dose of the hormonal agent that will be used in this trial will be the same one that the patient used before progression. Hormonal therapy may include any estrogen deprivation reagent such as Tamoxifen, Anastrazole, Exemestane, Letrozole, or Fulvestrant. All patients will receive Avastin (Bevacizumab) 15 mg/kg IV every three weeks. Based on statistical evaluations, 30 patients will be enrolled. The first evaluation of efficacy will be done at week 6; patients with objective response or stable disease will continue therapy with re-staging every 6 weeks until evidence of disease progression. Patients with progression of disease will be taken off study (see appendix A). PET scan will be done at baseline and only in the first evaluation (6 weeks) to obtain early "metabolic response data" that will be correlated with objective response and time to disease progression (PET data on week 6 will not be used to evaluate response and to make therapeutic decisions). PET "metabolic response" will be defined as a \>20% reduction in Standardized Uptake Value (SUV). Safety will be assessed by the recording of adverse events, serious adverse events, laboratory test results, and changes in vital signs. A positive response to Avastin (Bevacizumab) (reversal of hormonal resistance) will be defined as an objective response or stable disease of ≥ 3 months duration. All concomitant medication must be documented. Additionally, any diagnostic, therapeutic or surgical procedure performed during the study period, should be recorded including the date, indication, description of the procedure(s) and any clinical findings.

Arms: arm 1: The patient will continue the same hormonal therapy used prior to study enrollment but will combine it with Avastin.
Interventions: intervention 1: Avastin intervention 2: Hormonal therapy
Intervention descriptions: intervention 1: All patients will received Avastin 15 mg/kg IV every three weeks. The first evaluation will be done at Week 6. Patients with objective response or stable disease will continue therapy with restaging every 6 weeks until evidence of disease progression. Patients with progression of disease will be taken off study. intervention 2: aromatase inhibitor (letrozole 2.5mg/d PO, anastrazole 1mg/d PO, or exemestane 25mg/d PO)or Selective Estrogen Receptor Modulator (SERM) (tamoxifen 20mg/d PO)

Protocol documents: