The Role of Bisphosphonate and Simvastatin Combination on Therapeutic Response in Breast Cancer With Bone Metastasis Via Dicckopf-1 Pathway : A Randomised, Double-blind, Placebo Controlled Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Change in Serum DKK-1 Level
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •Written informed consent.
- •Serum creatinine ≤1.5 times normal range.
- •ALT ≤2 times normal range or total bilirubin ≤1.5 times normal range.
排除标准
- •Pregnancy or lactation.
- •Prior or ongoing simvastatin or other statin treatment.
- •Known hypersensitivity to bisphosphonates.
- •Allergy to statins.
研究组 & 干预措施
ZA + Simvastatin
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.
干预措施: Zoledronic Acid (Zometa) (Drug)
ZA + Placebo
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
干预措施: Placebo (Drug)
ZA + Placebo
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
干预措施: Zoledronic Acid (Zometa) (Drug)
ZA + Simvastatin
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.
干预措施: Simvastatin (Drug)
结局指标
主要结局
Change in Serum DKK-1 Level
时间窗: 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
次要结局
- 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))
研究者
Dr. dr. Erwin Danil Yulian, Sp.B (K) Onk
Principal Invesitagor, Oncological Surgeon
Indonesia University