Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
2017年4月9日 更新者：University of Southern California
POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)
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.
研究概览
详细说明
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.
ARM I: Patients receive zoledronic acid intravenously (IV) over 15 minutes on day 1.
ARM II: Patients receive zoledronic acid IV over 30 minutes on day 1.
After completion of study treatment, patients are followed up for 1 month.
研究类型
介入性
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
California
-
Los Angeles、California、美国、90033
- USC Norris Comprehensive Cancer Center
-
San Diego、California、美国、92121
- J.Craig Venter Institute-San Diego
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：诊断
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
|
相关研究
其他名称：
鉴于IV
其他名称：
|
|
实验性的：Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
|
相关研究
其他名称：
鉴于IV
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
大体时间：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.
|
Up to 1 month
|
|
Urine concentrations of Zol collected at visits 2, 3, 4, and 5
大体时间：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.
|
Up to 1 month
|
|
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
大体时间：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.
|
Up to 1 month
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Identify potential risk factors for BRONJ
大体时间：Up to1 month
|
The magnitude of associations between the study variables and BRONJ status will be estimated.
For categorical variables, the univariate association with each variable and with BRONJ will be determined using Wald's test of association.
For continuous variables, the association with each variable and BRONJ will be determined using Wald's test.
Logistic regression will be used to evaluate the risk of BRONJ for development of the final risk model.
|
Up to1 month
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Parish Sedghizadeh、University of Southern California
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (预期的)
2016年6月1日
初级完成 (预期的)
2020年12月1日
研究完成 (预期的)
2021年6月1日
研究注册日期
首次提交
2014年2月7日
首先提交符合 QC 标准的
2014年2月19日
首次发布 (估计)
2014年2月24日
研究记录更新
最后更新发布 (实际的)
2017年4月11日
上次提交的符合 QC 标准的更新
2017年4月9日
最后验证
2017年4月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.