Clinical trial NCT02069340: 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
Overall status: WITHDRAWN
Phase: NA
Conditions: Malignant Neoplasm
Musculoskeletal Complications
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-02-24
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
timeFrame: Up to 1 month
measure: Urine concentrations of Zol collected at visits 2, 3, 4, and 5
timeFrame: Up to 1 month
measure: Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
timeFrame: Up to 1 month
Secondary outcomes:
measure: Identify potential risk factors for BRONJ
timeFrame: Up to1 month
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: J.Craig Venter Institute-San Diego
state: California
Study officials:
affiliation: University of Southern California
name: Parish Sedghizadeh
role: PRINCIPAL_INVESTIGATOR
References: