POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
研究概览
简要总结
This randomized clinical trial studies genetics in predicting risk of bisphosphonate-related osteonecrosis of the jaw in patients with cancer receiving zoledronic acid. Zoledronic acid is an anti-resorptive drug used as part of cancer treatment. A serious side effect of these drugs is death of the jawbone, commonly called bisphosphonate-related osteonecrosis of the jaw (BRONJ). Genetic research may help doctors understand risk factors for BRONJ or who is more likely to get BRONJ and why.
详细描述
PRIMARY OBJECTIVES:
I. To develop a pharmacometric model to predict jawbone zoledronic acid (Zol) concentrations in oncologic patients by conducting a prospective cohort study of Zol pharmacometrics in BRONJ patients, measuring drug in plasma, urine, and jawbone tissue obtained during surgical treatment for BRONJ.
SECONDARY OBJECTIVES:
I. To clinically assess and validate our predictive pharmacometric model, and develop a risk model for BRONJ in oncologic patients receiving intravenous Zol.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PATIENTS WITH BRONJ:
- •All cancer patients > 18 years of any ethnicity who have been treated with intravenous zoledronate (zoledronic acid) for >=1 year duration
- •Clinical diagnosis of BRONJ subsequent to oral surgery as established by standard clinical protocol per American Association of Oral and Maxillofacial Surgeons (AAOMS) diagnostic criteria
- •Willingness to have photographs taken to document lesions
- •Consent for sample collection for urine, hematology, histopathology and microbial profiling
- •Cognitively able and willing to provide consent
- •Have a World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance score =< 2 and life expectancy > 6 months
- •PATIENTS WITHOUT BRONJ:
- •Cancer patients without BRONJ who have been treated with intravenous zoledronate for >= 1 year duration
- •No signs or symptoms of BRONJ
- •Willingness to provide consent for sample collection for blood, urine and saliva
排除标准
- •WHO/ECOG performance score > 2 and life expectancy of < 6 months
- •Coagulopathy
- •Active systemic infection or autoimmune disease
- •Currently pregnant or within 3 months post-partum, or unwilling to undergo pregnancy testing or report possible pregnancy promptly
- •Severe cardiovascular, pulmonary or other systemic conditions that prevent participation in the study
- •Salivary gland hypofunction regardless of underlying pathology
- •Neutropenia (serum absolute neutrophil count [ANC] < 1,000/uL)
- •Cognitive, language or hearing problems
- •Renal disease, and we will use a calculated serum creatinine clearance over 30 ml/min at the screening appointment as an exclusion criteria
- •Participation in another research project that might interfere with completion of this study
- •Patients undergoing active antibiotic therapy
研究组 & 干预措施
Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
干预措施: zoledronic acid (Drug)
Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
干预措施: pharmacological study (Other)
Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
干预措施: zoledronic acid (Drug)
Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
干预措施: pharmacological study (Other)
结局指标
主要结局
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
时间窗: Up to 1 month
Data will be iteratively fit to the model using non-parametric modeling, simulation, and clinical dosing software. The parameters will be estimated, as well as their relationships to each other. Each measured patient concentration is Fisher weighted.
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
时间窗: Up to 1 month
Data will be iteratively fit to the model using non-parametric modeling, simulation, and clinical dosing software. The parameters will be estimated, as well as their relationships to each other. Each measured patient concentration is Fisher weighted.
Urine concentrations of Zol collected at visits 2, 3, 4, and 5
时间窗: Up to 1 month
Data will be iteratively fit to the model using non-parametric modeling, simulation, and clinical dosing software. The parameters will be estimated, as well as their relationships to each other. Each measured patient concentration is Fisher weighted.
次要结局
- Identify potential risk factors for BRONJ(Up to1 month)