A Multicenter Phase II Study, to Evaluate the Predictive Markers of Response in Locally Advanced Breast Cancer, Treated With Bevacizumab Combined With Neoadjuvant Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 22
- 主要终点
- Evaluation of SNPs genotyping.
研究概览
简要总结
The purpose of this study is to compare the association between image and certain molecular markers with complete response in patients with locally advanced breast cancer, treated with neoadjuvant chemotherapy composed of Bevacizumab, Docetaxel and Doxorubicin.
详细描述
This is a pharmacogenomic phase II, multicenter, prospective clinical trial whose main objective is to evaluate the association of molecular and imaging markers with the response to bevacizumab administration in combination with docetaxel and doxorubicin as neoadjuvant chemotherapy in patients diagnose with locally advanced breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed consent form
- •Ages between 18 and 70
- •12 months of life expectancy at least
- •Histologically confirmed breast cancer
- •No previous treatment for locally advanced breast cancer
- •Her2+ o Her2-
- •Disease measurable by PET and/or MRI
- •Adequate organic function
- •Negative pregnancy test; fertile women must use anticonceptive methods after ICF and 30 days after last study drug administration
- •Enough capability to follow the procedures and follow-up test included in the protocol
排除标准
- •Metastatic disease
- •Inadequate health to receive the study chemotherapy
- •Previous breast cancer treatment
- •Pregnant or lactating women
- •Major surgery or significative traumatic injure in the 28 days previous to inclusion, or during treatment.
- •Minor surgery 24 hours before first bevacizumab infusion
- •Concomitant or recent aspirin(>325mg/day)or clopidogrel(>75mg/day) treatment
- •Concomitant or recent oral anticoagulant treatment
- •History or evidence or bleeding diathesis or hereditary coagulopathy with bleeding risk
- •Uncontrolled arterial hypertension
- •Clinical significative heart disease, or uncontrolled severe arrhythmia disorder
- •Unhealed wounds, peptic ulcer or bone fracture
- •History of abdominal fistula, gastrointestinal perforation or intrabdominal abscess, 6 months before inclusion
- •Evidence of any other disease, neurological or metabolical disorder or physical examination or laboratory finding related with any disease that makes the subjet ineligible for the study treatment or that put the subject in risk because of the study treatment.
- •Psychiatric disorders that may prevent the subject to complete the study treatment
- •Current participation in any other trial involving an investigational drug, or participation in any kind of trial 28 days before inclusion
- •Chronical corticosteroid treatment
- •Hypersensitivity reaction to bevacizumab or any of its components or any of the other study drugs or components
- •Patients diagnosed with different neoplasms the previous 5 years excluding non melanoma skin cancer and resected cervical cancer
结局指标
主要结局
Evaluation of SNPs genotyping.
时间窗: This evaluation will be performed within 14 days before start of treatment
The analysis of genetic differences will be determined through analysis of single nucleotide polymorphisms. It will be assesed before starting the treatment using Affymetrix's Human Mapping 500k array set.
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)
时间窗: This evaluation will be performed within 12-19 days aftet fifth cycle.
The radiological interpretation of the images will evaluate size, shape, extent, distribution and kinetics of the lesons according to American College of Radiology Breast Imaging Reporting and Data System (ACR BIRADS- MRI (2003) guidelines).
Positron emission tomography (PET) scan
时间窗: This evaluation will be performed within 12-19 days aftet fifth cycle
It will be determined the association between tissue:blood activity ratio and hypoxic tumor volume by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). DNA synthesis, assesed by \[18F\]-fluoro-3'-deoxy-3'-L-fluorothymidine PET (FLT-PET), will be compared to quantitative kinetics data adquired through previously described DCE-MRI. Finally, these results will be correlated with the Risk Score obtained in the genomic analysis
Evaluation of Genomic tissular profile in a sample of biopsy
时间窗: This evaluation will be performed within 12-19 days aftet fifth cycle
A correlative analysis will be performed between the expression profile of the sample obtained by Affymetrix 's GeneChip Human Genome U133 and its association with tumor response (based on the imaging markers described previously) on the proposed stages (baseline, before first cycle of treatment and after fifth cycle of treatment).
Evaluation of Proteomic expression in blood serum
时间窗: This evaluation will be performed within 12-19 days aftet fifth cycle.
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
次要结局
- Evaluation of Complete pathological response in surgical piece(This evaluation will be performed within 20-22 weeks after start of treatment.)