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

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.

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