The Role of Bisphosphonate and Simvastatin Combination on Therapeutic Response in Breast Cancer With Bone Metastasis Via Dicckopf-1 Pathway

NCT07823751 | Completed DMC

• 1 other identifier: IndonesiaU2021
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This randomised, double-blind, placebo-controlled pilot trial evaluated the therapeutic response of zoledronic acid combined with simvastatin in women with breast cancer and confirmed bone metastases. Participants were randomized to receive zoledronic acid plus simvastatin 40 mg daily or zoledronic acid plus placebo for six treatment cycles. Clinical response, bone scan response, bone turnover biomarkers, and treatment-related safety and tolerability were evaluated. The study was designed as a pilot trial and was not powered to establish definitive efficacy.

Conditions

Breast Cancer With Bone Metastasis

Keywords

Breast Cancer; Bone Metastasis; Zoledronic Acid; Simvastatin; Biphosphonate; Dickkopf-1; Dkk-1; TRACP-5b

Outcome Measures

Primary Outcomes (1)

• Change in Serum DKK-1 Level

  Change in serum Dkk-1 concentration from baseline to the end of treatment following six treatment cycles

  Baseline to the end of Cycle 6 (each cycle is 21 days)

Secondary Outcomes (4)

• Change in VAS pain Score

  Baseline, end of Cycle 3, and end of Cycle 6 (each cycle is 21 days)

• Bone Scan Response

  At the end of Cycle 6 (each cycle is 21 days)

• Change in serum TRAcP-5b level

  Baseline to the end of Cycle 6 (each cycle is 21 days)

• Safety and Tolerability

  Throughout the six treatment cycles (each cycle is 21 days)

Study Arms (2)

ZA + Simvastatin

EXPERIMENTAL

Participants received zoledronic acid combined with simvastatin 40 mg daily for six treatment cycles. Each cycle was separated by three weeks, and simvastatin was administered at night.

Drug: Simvastatin; Drug: Zoledronic Acid (Zometa)

ZA + Placebo

PLACEBO COMPARATOR

Participants received zoledronic acid combined with placebo for six treatment cycles. Each cycle was separated by three weeks, and placebo was administered daily at night

Drug: Placebo; Drug: Zoledronic Acid (Zometa)

Interventions

Simvastatin DRUG

Simvastatin 40 mg was administered orally once daily at night for six treatment cycles, with each cycle separated by three weeks, in combination with zoledronic acid

ZA + Simvastatin

Placebo DRUG

An identical placebo tablet was administered orally once daily at night for six treatment cycles, with each cycle separated by three weeks, in combination with zoledronic acid.

ZA + Placebo

Zoledronic Acid (Zometa) DRUG

Zoledronic acid 4 mg was administered as an intravenous infusion over 15 minutes for six treatment cycles, with each cycle separated by three weeks.

ZA + Placebo; ZA + Simvastatin

Eligibility Criteria

• Age: 19 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women diagnosed with breast cancer with confirmed bone metastasis based on bone scan.
• Previously received systemic chemotherapy.
• Scheduled to initiate bisphosphonate therapy as part of standard oncologic management.
• Age \>18 years.
• ECOG performance status ≤1.
• Written informed consent.
• Serum creatinine ≤1.5 times normal range.
• ALT ≤2 times normal range or total bilirubin ≤1.5 times normal range.

You may not qualify if:

• Pregnancy or lactation.
• Prior or ongoing simvastatin or other statin treatment.
• Known hypersensitivity to bisphosphonates.
• Allergy to statins.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Dr. Cipto Mangunkusumo National General Hospital / Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Jakarta Pusat, DKI Jakarta, 10430, Indonesia

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Simvastatin; Zoledronic Acid

Condition Hierarchy (Ancestors)

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; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alvita Dewi Siswoyo, MD

  Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

  STUDY DIRECTOR

• Muhammad Ilyas, MD

  cOccupational Medicine Division, Department of Community Medicine, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

  STUDY DIRECTOR

• Matahari Widyarani, MD

  dGeneral Practitioner, Research Assistant in Surgical Oncology Division, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Invesitagor, Oncological Surgeon

Model Details: Participants were randomly assigned to one of two parallel treatment groups: zoledronic acid plus simvastatin or zoledronic acid plus placebo. Both groups received treatment for six cycles, with each cycle separated by three weeks.

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 16, 2026
• Study Start: April 10, 2021
• Primary Completion: April 10, 2023
• Study Completion: June 20, 2026
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)