Clinical Trial: Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)

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 Summary:

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.


Sponsor: University of Southern California

Current Primary Outcome:

  • 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.
  • 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.
  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome: 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.


Original Secondary Outcome: Same as current

Information By: University of Southern California

Dates:
Date Received: February 7, 2014
Date Started: June 2016
Date Completion: June 2021
Last Updated: April 9, 2017
Last Verified: April 2017