Breast Cancer With Bone Metastasis
Conditions
Keywords
Breast Cancer, Bone Metastasis, Zoledronic Acid, Simvastatin, Biphosphonate, Dickkopf-1, Dkk-1, TRACP-5b
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.
Detailed description
This was a prospective, single-center, randomized, double-blind, placebo-controlled pilot trial involving women with breast cancer and confirmed bone metastases. Participants were randomized to receive either zoledronic acid (ZA) in combination with simvastatin 40 mg daily or ZA with placebo for six treatment cycles. Zoledronic acid 4 mg was administered by intravenous infusion over 15 minutes. Simvastatin 40 mg or an identical placebo tablet was administered orally once daily at night. Each treatment cycle was separated by three weeks. Placebo tablets were prepared by the hospital pharmacy to be identical in appearance, size, and colour to simvastatin tablets. Treatment allocation was concealed from both patients and investigators throughout the study. Patient adherence to the oral medication was monitored using self-reported patient diaries reviewed at each clinic visit. Clinical efficacy was assessed using the Visual Analog Scale (VAS) pain score. Radio-imaging efficacy was evaluated using bone scintigraphy according to the MD Anderson criteria. Biological efficacy was assessed by measuring serum Dkk-1 and TRACP-5b at baseline and after the sixth treatment cycle. Safety and tolerability were evaluated throughout treatment using clinical and laboratory assessments, with adverse events graded according to CTCAE version 4.03. As a pilot trial, the study was not powered to establish definitive efficacy. The estimates were intended to inform the design and sample size of a future adequately powered trial.
Interventions
DRUGSimvastatin
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
DRUGPlacebo
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.
Zoledronic acid 4 mg was administered as an intravenous infusion over 15 minutes for six treatment cycles, with each cycle separated by three weeks.
Sponsors
Indonesia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
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.
Eligibility
Sex/Gender
FEMALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* Pregnancy or lactation. * Prior or ongoing simvastatin or other statin treatment. * Known hypersensitivity to bisphosphonates. * Allergy to statins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum DKK-1 Level | Baseline to the end of Cycle 6 (each cycle is 21 days) | Change in serum Dkk-1 concentration from baseline to the end of treatment following six treatment cycles |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in VAS pain Score | Baseline, end of Cycle 3, and end of Cycle 6 (each cycle is 21 days) | Pain was assessed using the Visual Analog Scale (VAS), ranging from 0 to 10, with higher scores indicating greater pain. |
| Bone Scan Response | At the end of Cycle 6 (each cycle is 21 days) | Bone scan response categorized as responsive, stable disease, or progressive disease. |
| Change in serum TRAcP-5b level | Baseline to the end of Cycle 6 (each cycle is 21 days) | Change in serum TRACP-5b concentration from baseline to the end of treatment. |
| Safety and Tolerability | Throughout the six treatment cycles (each cycle is 21 days) | Incidence and severity of treatment-related adverse events during the study, including hematological, non-hematological, musculoskeletal, renal, bisphosphonate-related, and statin-associated toxicities. Adverse events were graded according to CTCAE version 4.03. |
Countries
Indonesia
Contacts
STUDY_DIRECTORAlvita Dewi Siswoyo, MD
Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
STUDY_DIRECTORMuhammad Ilyas, MD
cOccupational Medicine Division, Department of Community Medicine, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
STUDY_CHAIRMatahari Widyarani, MD
dGeneral Practitioner, Research Assistant in Surgical Oncology Division, Faculty of Medicine, Universitas Indonesia-dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Outcome results
None listed