Gene Expression Profiles of Breast Cancer Treated With Sequential Adriamycin and Docetaxel in Relation to Tumor Responses
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- 1. Evaluate the impact of adriamycin and docetaxel on tumor gene expression profiles.
研究概览
简要总结
We hypothesize that changes in tumor gene expression profiles vary in response to different sequences and types of chemotherapy, and that gene expression changes will correlate with tumor response. We are also looking to correlate drug pharmacokinetics and treatment toxicity with genotype of drug metabolizing enzymes and tranporters.Patients with metastatic breast cancer and who have measurable primary breast tumor will be randomized to one of two alternating sequences of adriamycin and docetaxel. Serial tumor biopsies and plasma samples will be obtained for gene expression and proteomic studies to identify biomarkers that will predict for chemotherapy response.
详细描述
Significant inter-individual variation exists in tumor response and chemotherapy toxicity because of unique tumor and patient factors. Individual drugs with distinct mechanisms of action may induce specific genomic and proteomic changes that may be used as predictor for response. We plan to study serial genomic and proteomic profiles in primary breast tumor treated with one of two sequences of alternating adriamycin (A) and docetaxel (T), A>T>A>T>A>T, or T>A>T>A>T>A, at 75mg/m2 3 weekly for each drug. Pharmacokinetic analysis of both drugs will be performed; amplified tumor RNA will be hybridized on Affymetrix® HG-U133+2 array; tumor proteins will be fractionated and profiled with ProteinChip® Array SELDI MS (Ciphergen). Tumor gene expression and proteomic changes will be correlated with treatment response to identify biomarkers that may predict chemotherapy sensitivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, age > 18 years.
- •Histologic or cytologic diagnosis of breast carcinoma.
- •Stage II to IV breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- •Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- •Karnofsky performance status of 70 or higher.
- •Estimated life expectancy of at least 12 weeks.
- •Adequate organ function including the following:
- •Bone marrow: White blood cells (WBC) >= 3.5 x 109/L Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100 x 109/L Haemoglobin >= 9g/dL
- •Hepatic: Bilirubin <= 1.5 x upper limit of normal (ULN), ALT or AST <= 2.5x ULN, (or <=5 X with liver metastases) Alkaline phosphatase <= 2.5x ULN.
- •Renal: creatinine <= 1.5x ULN
- •Adequate cardiac function
- •Signed informed consent from patient or legal representative.
- •Patients with reproductive potential must use an approved contraceptive method if appropriate (eg, intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
排除标准
- •Prior treatment for locally advanced or metastatic breast cancer.
- •Treatment within the last 30 days with any investigational drug.
- •Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- •Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- •Pregnancy.
- •Breast feeding.
- •Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- •Poorly controlled diabetes mellitus.
- •Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- •Symptomatic brain metastasis.
- •History of significant neurological or mental disorder, including seizures or dementia.
- •Peripheral neuropathy of >= CTC grade
- •History of hypersensitivity to drugs formulated in Tween 80, the vehicle used for commercial docetaxel formulations.
结局指标
主要结局
1. Evaluate the impact of adriamycin and docetaxel on tumor gene expression profiles.
2. Correlate overall tumor response with tumor gene expression profiles.
次要结局
- To correlate adriamycin and docetaxel pharmacokinetics with:
- 1. Genetic polymorphisms of MDR-1, Cyp3A and GSTs.
- 2. Drug toxicity and tumor response.