NCT05550415

The Role of Simvastatin in the Epithelial-Mesenchymal Transition Process of Breast Cancer

Vimentin Expression-based Therapeutic Response in Triple Negative Breast Cancer Receiving Combination of Simvastatin and NAC: a Randomized, Double-Blind, Placebo-Controlled Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: Indonesia University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Triple Negative Breast Cancer
• Chemotherapy Effect
• Simvastatin Adverse Reaction

Interventions

Type	Name	Description
DRUG	Simvastatin 40mg	The administration of Simvastatin 40 mg in addition to ACT regiment of neoadjuvant chemotherapy
DRUG	Placebo	The administration of Placebo capsule 40 mg in addition to ACT regiment of neoadjuvant chemotherapy

Timeline

• Start date: 2022-08-19
• Primary completion: 2025-05-01
• Completion: 2025-08-01
• First posted: 2022-09-22
• Last updated: 2024-10-03

Locations

1 site across 1 country: Indonesia