Vimentin Expression-based Therapeutic Response in Triple Negative Breast Cancer Receiving Combination of Simvastatin and NAC: a Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Vimentin Expression
研究概览
简要总结
Introduction: Most cases of Triple Negative Breast Cancer (TNBC) have a high proliferation rate. TNBC is associated with a poor prognosis, a high recurrence rate, and a high incidence of distant metastases. The Epithelial-Mesenchymal Transition process (EMT) plays an essential role in the metastatic process. EMT markers were also more abundant in TNBC and contributed to a poorer TNBC prognosis. As an important EMT marker, the increased expression of vimentin also contributed to the increase in TNBC aggressiveness and resistance to chemotherapeutic agents. Through the mechanism of action in inhibiting the mevalonate pathway, statins can help inhibit the EMT process in metastases. Notably, simvastatin promotes the down-regulation of vimentin in breast cancer cells. The combination of statins and neoadjuvant chemotherapy (NAC) improves the cancer patient's response. This study is expected to evaluate the role of a combination between NAC and simvastatin on therapeutic response in TNBC patients through vimentin expression.
Methods: This study is a double-blind, randomized, placebo-controlled trial conducted in Dr. Cipto Mangunkusumo National Central General Hospital. An expected total of 26 TNBC patients will be assessed for eligibility and asked for informed consent. Patients with the plan to have ACT (Doxorubicin hydrochloride, Cyclophosphamide, Paclitaxel) chemotherapy regimen will receive either a combination of ACT-Simvastatin (40 mg/day) or ACT-Placebo. The biopsy will be taken pre-NAC to make the histopathological diagnosis and examine the expression of vimentin. Patients will be evaluated for adverse effects reaction every cycle and the clinical response after 8 cycles. The post-intervention biopsy will be conducted after the cycle finish. The pathological response and vimentin expression will be reviewed from the obtained samples.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients with advanced breast cancer (locally advanced and distantly advanced) with triple-negative molecular type confirmed by biopsy and immunohistochemical examination.
- •The patient planned to receive 8 cycles of AC-T chemotherapy.
- •Patient age > 18 years.
- •Willing to participate in research by signing informed consent.
排除标准
- •The patient is pregnant or breastfeeding.
- •Patients who have received chemotherapy or are on simvastatin therapy.
- •Allergy to statins.
研究组 & 干预措施
Simvastatin
The group received standard treatment with simvastatin 40mg in capsule by oral route, once a day, for 21 days (every cycle of the chemotherapy regiment)
干预措施: Simvastatin 40mg (Drug)
Placebo
The group received standard treatment with placebo 40mg in capsule by oral route, once a day, for 21 days (every cycle of the chemotherapy regiment)
干预措施: Placebo (Drug)
结局指标
主要结局
Vimentin Expression
时间窗: 6 months
Vimentin expression is measured based on Histoscore (H-Score) with immunohistochemistry examination: * 0-50 : negative (0) * 51-100 : weak positive (1+) * 101-200 : moderate positive (2+) * 201-300 : strong positive (3+)
次要结局
- Pathological Response(6 months)
- Clinical Response(6 months)
研究者
Dr. dr. Erwin Danil Yulian, Sp.B (K) Onk
Head of Research Program, Division of Surgical Oncology
Indonesia University