Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
Primary Purpose
Malignant Neoplasm, Musculoskeletal Complications
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
zoledronic acid
pharmacological study
Sponsored by
About this trial
This is an interventional diagnostic trial for Malignant Neoplasm
Eligibility Criteria
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
Sites / Locations
- USC Norris Comprehensive Cancer Center
- J.Craig Venter Institute-San Diego
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm I (zoledronic acid over 15 minutes)
Arm II (zoledronic acid over 30 minutes)
Arm Description
Patients receive zoledronic acid IV over 15 minutes on day 1.
Patients receive zoledronic acid IV over 30 minutes on day 1.
Outcomes
Primary Outcome Measures
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
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
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.
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
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.
Secondary Outcome Measures
Identify potential risk factors for BRONJ
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.
Full Information
NCT ID
NCT02069340
First Posted
February 7, 2014
Last Updated
April 9, 2017
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02069340
Brief Title
Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
Official Title
POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Withdrawn
Study Start Date
June 2016 (Anticipated)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
June 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Neoplasm, Musculoskeletal Complications
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (zoledronic acid over 15 minutes)
Arm Type
Experimental
Arm Description
Patients receive zoledronic acid IV over 15 minutes on day 1.
Arm Title
Arm II (zoledronic acid over 30 minutes)
Arm Type
Experimental
Arm Description
Patients receive zoledronic acid IV over 30 minutes on day 1.
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
CGP 42446, CGP42446A, NDC-zoledronate, zoledronate, Zometa
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
Description
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.
Time Frame
Up to 1 month
Title
Urine concentrations of Zol collected at visits 2, 3, 4, and 5
Description
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.
Time Frame
Up to 1 month
Title
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
Description
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.
Time Frame
Up to 1 month
Secondary Outcome Measure Information:
Title
Identify potential risk factors for BRONJ
Description
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.
Time Frame
Up to1 month
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Parish Sedghizadeh
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
J.Craig Venter Institute-San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92121
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
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