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

Triple Negative Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05550415
• Other study ID #: IndonesiaU2022
• Status: Recruiting
• Phase: Phase 2
• Start date: August 19, 2022
• Est. completion date: February 2025

Study information

• Verified date: September 2022
• Source: Indonesia University
• Contact: Erwin D Yulian, MD
• Phone: +6281315249627
• Email: erwin.yulian[@]ui.ac.id
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: February 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Simvastatin 40mg
The administration of Simvastatin 40 mg in addition to ACT regiment of neoadjuvant chemotherapy
• Placebo
The administration of Placebo capsule 40 mg in addition to ACT regiment of neoadjuvant chemotherapy

Locations

Country	Name	City	State
Indonesia	Dr. Cipto Mangunkusumo National Central General Hospital	Jakarta Pusat	DKI Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

Outcome

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