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

NCT05550415 | Recruiting Phase 2 DMC

• 1 other identifier: IndonesiaU2022
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Triple Negative Breast Cancer; Chemotherapy Effect; Simvastatin Adverse Reaction

Keywords

Vimentin; Simvastatin; Epithelial-Mesenchymal Transition; Neoadjuvant Chemotherapy; Clinical Response; Pathological Response

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Pathological Response

  6 months

• Clinical Response

  6 months

Study Arms (2)

Simvastatin

EXPERIMENTAL

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)

Drug: Simvastatin 40mg

Placebo

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

Simvastatin 40mg DRUG

The administration of Simvastatin 40 mg in addition to ACT regiment of neoadjuvant chemotherapy

Also known as: Simvastatin

Simvastatin

Placebo DRUG

The administration of Placebo capsule 40 mg in addition to ACT regiment of neoadjuvant chemotherapy

Also known as: Placebo oral capsule 40 mg

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Dr. Cipto Mangunkusumo National Central General Hospital

Jakarta Pusat, DKI Jakarta, 10430, Indonesia

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Erwin D Yulian, MD

  Surgical Oncology Division, Department of Surgery, Universitas Indonesia

  PRINCIPAL INVESTIGATOR

• Tantri Hellyanti, MD

  Department of Pathological Anatomy, Universitas Indonesia

  STUDY DIRECTOR

• Shabrina Adzania, MD

  Research Assistant, Department of Surgery, Universitas Indonesia

  STUDY CHAIR

Central Study Contacts

Erwin D Yulian, MD

CONTACT

+6281315249627; erwin.yulian@ui.ac.id

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Research Program, Division of Surgical Oncology

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: August 19, 2022
• Primary Completion: May 1, 2025
• Study Completion: August 1, 2025
• Last Updated: October 3, 2024

Record last verified: 2024-10

Locations

ID (1)