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

NCT ID: NCT02069340

Last Updated: 2017-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-30

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Malignant Neoplasm Musculoskeletal Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Arm I (zoledronic acid over 15 minutes)

Patients receive zoledronic acid IV over 15 minutes on day 1.

Group Type EXPERIMENTAL

zoledronic acid

Intervention Type DRUG

Given IV

pharmacological study

Intervention Type OTHER

Correlative studies

Arm II (zoledronic acid over 30 minutes)

Patients receive zoledronic acid IV over 30 minutes on day 1.

Group Type EXPERIMENTAL

zoledronic acid

Intervention Type DRUG

Given IV

pharmacological study

Intervention Type OTHER

Correlative studies

Interventions

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zoledronic acid

Given IV

Intervention Type DRUG

pharmacological study

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CGP 42446 CGP42446A NDC-zoledronate zoledronate Zometa pharmacological studies

Eligibility Criteria

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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
* Participation in another research project that might interfere with completion of this study
* Patients undergoing active antibiotic therapy
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Parish Sedghizadeh

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

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USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

J.Craig Venter Institute-San Diego

San Diego, California, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2014-00207

Identifier Type: REGISTRY

Identifier Source: secondary_id

0S-13-3

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0S-13-3

Identifier Type: -

Identifier Source: org_study_id

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