A Phase II Neo-Adjuvant Study of Cisplatin, Paclitaxel With or Without RAD001 in Patients With Triple-negative Locally Advanced Breast Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 8
- 主要终点
- Number of Patients With Pathological Complete Response
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving chemotherapy together with everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether cisplatin and paclitaxel are more effective when given together with or without everolimus in treating patients with breast cancer.
PURPOSE: This randomized phase II trial is studying how well cisplatin and paclitaxel work when given together with or without everolimus in treating patients with stage II or stage III breast cancer.
详细描述
OBJECTIVES:
Primary
- To determine the pathological complete response in patients with triple-negative, stage II or III breast cancer treated with neoadjuvant cisplatin and paclitaxel with or without everolimus.
Secondary
- To determine the safety profile of these treatment regimens.
- To evaluate tumor response to these treatment regimens as measured by ultrasound before definitive surgery.
- To evaluate the rate of breast conservation surgery after treatment with these regimens.
- To determine treatment-mediated changes in cell cycle position, proliferation, and apoptosis as well as status, levels, and phosphorylation state of S6K, p53, p73, and p63 and select p53 family target genes before and after initiation of paclitaxel.
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a pre-treatment gene signature that will predict response.
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a change in gene signature after the first treatment that will predict response.
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if previously established p63 and p73 gene signatures predict response to treatment.
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if a change will be observed in p63 and p73 gene signatures between pre- and post-treatment biopsies.
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if triple-negative breast cancers can be clustered into different subtypes on the basis of gene expression, given the size of the microarray data set that will be generated from this clinical trial and previous clinical trials (> 100 tumors).
- To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if p63 and p73 gene signatures can sub-classify triple-negative breast cancers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Locally recurrent breast cancer.
- •Pregnant or lactating women.
- •Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
- •Use of CYP3A4 modifiers (Appendix A)
- •Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
- •History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible.
- •History of hepatitis B or hepatitis C. If patient is judged to be at risk for having had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed (i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)
- •Active or uncontrolled infection requiring parenteral antibiotics.
- •Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- •Symptomatic neuropathy (≥ grade 2).
- •Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones specified in the protocol.
- •Concurrent treatment with an investigational agent.
- •Used an investigational drug within 15 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy.
研究组 & 干预措施
Cisplatin and Paclitaxel + RAD001
Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks
干预措施: cisplatin (Drug)
Cisplatin and Paclitaxel + RAD001
Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks
干预措施: everolimus (Drug)
Cisplatin and Paclitaxel + RAD001
Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks
干预措施: paclitaxel (Drug)
Cisplatin and Paclitaxel + RAD001
Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks
干预措施: Venous blood draw (Procedure)
Cisplatin and Paclitaxel + Placebo
Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
干预措施: cisplatin (Drug)
Cisplatin and Paclitaxel + Placebo
Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
干预措施: paclitaxel (Drug)
Cisplatin and Paclitaxel + Placebo
Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
干预措施: placebo (Other)
Cisplatin and Paclitaxel + Placebo
Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
干预措施: Venous blood draw (Procedure)
结局指标
主要结局
Number of Patients With Pathological Complete Response
时间窗: at time of surgery, week 15-18
Pathological complete response is defined as no residual tumor on histopathological analysis of both breast and axillary contents.
次要结局
- Number of Patients With Each Worst-grade Toxicity Response(week 12)
- Number of Patients That Underwent Breast Conservation Surgery(at the time of surgery, week 15-18)
- Clinical Tumor Response to Neoadjuvant Therapy as Measured by Ultrasound Immediately Before Surgery(After treatment, week 12-15)
研究者
Ingrid Mayer, MD
Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist
Vanderbilt-Ingram Cancer Center