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

Phase 2

Recruiting

• Conditions: Triple Negative Breast Cancer; Chemotherapy Effect; Simvastatin Adverse Reaction
• Interventions: Drug: Simvastatin 40mg; Drug: Placebo

• Registration Number: NCT05550415
• Lead Sponsor: Indonesia University

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-19
• Study First Submitted: 2022-09-19
• Study First Submitted QC: 2022-09-19
• Study First Posted: 2022-09-22
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-03
• Primary Completion: 2025-05
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 26

Inclusion Criteria

1. Female patients with advanced breast cancer (locally advanced and distantly advanced) with triple-negative molecular type confirmed by biopsy and immunohistochemical examination.
2. The patient planned to receive 8 cycles of AC-T chemotherapy.
3. Patient age > 18 years.
4. Willing to participate in research by signing informed consent.

Exclusion Criteria

1. The patient is pregnant or breastfeeding.
2. Patients who have received chemotherapy or are on simvastatin therapy.
3. Allergy to statins.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin 40mg	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)
Placebo	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)

Primary Outcome Measures

Name	Time	Method
Vimentin Expression	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+)

Secondary Outcome Measures

Name	Time	Method
Pathological Response	6 months	Pathological Response as Measured by Miller-Payne system; Evaluation before and after chemotherapy, divided into: 1. Grade 1: There is no significant change or reduction in cancer cells.; 2. Grade 2: Reduction of \<30% cancer cells; 3. Grade 3: Reduction of cancer cells between 30-90%; 4. Grade 4: Reduction of \> 90% cancer cells; 5. Grade 5 : There are no residual cancer cells. DCIS (Ductal Carcinoma In Situ) might be detected.
Clinical Response	6 months	Clinical response based on WHO (World Health Organization) criteria: 1. Complete Response (CR): Disappearance; 2. Partial Response (PR): 50% decrease; 3. Stable Disease(SD): Neither PR nor PD criteria met; 4. Progressive Disease (PD):25% increase; no CR, PR, or SD documented before increased disease

Trial Locations

Locations (1)

Dr. Cipto Mangunkusumo National Central General Hospital; 🇮🇩 Jakarta Pusat, DKI Jakarta, Indonesia