Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
April 9, 2017 updated by: 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.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- USC Norris Comprehensive Cancer Center
-
San Diego, California, United States, 92121
- J.Craig Venter Institute-San Diego
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
|
Correlative studies
Other Names:
Given IV
Other Names:
|
|
Experimental: Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
|
Correlative studies
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
Time Frame: 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
Time Frame: 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
Time Frame: 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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Identify potential risk factors for BRONJ
Time Frame: 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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Parish Sedghizadeh, University of Southern California
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
June 1, 2016
Primary Completion (Anticipated)
December 1, 2020
Study Completion (Anticipated)
June 1, 2021
Study Registration Dates
First Submitted
February 7, 2014
First Submitted That Met QC Criteria
February 19, 2014
First Posted (Estimate)
February 24, 2014
Study Record Updates
Last Update Posted (Actual)
April 11, 2017
Last Update Submitted That Met QC Criteria
April 9, 2017
Last Verified
April 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0S-13-3 (Other Identifier: USC Norris Comprehensive Cancer Center)
- P30CA014089 (U.S. NIH Grant/Contract)
- NCI-2014-00207 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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