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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by University of Southern California
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT02069340
First received: February 7, 2014
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Malignant Neoplasm
Musculoskeletal Complications
Drug: zoledronic acid
Other: pharmacological study

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Plasma concentrations of Zol collected at visits 2, 3, 4, and 5 [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to1 month ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 100
Study Start Date: March 2014
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
Drug: zoledronic acid
Given IV
Other Names:
  • CGP 42446
  • CGP42446A
  • NDC-zoledronate
  • zoledronate
  • Zometa
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
Drug: zoledronic acid
Given IV
Other Names:
  • CGP 42446
  • CGP42446A
  • NDC-zoledronate
  • zoledronate
  • Zometa
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02069340

Locations
United States, California
USC Norris Comprehensive Cancer Center Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Parish Sedghizadeh    213-740-2704    sedghiza@usc.edu   
Principal Investigator: Parish Sedghizadeh         
J.Craig Venter Institute-San Diego Not yet recruiting
San Diego, California, United States, 92121
Contact: Shibu Yooseph    858-200-1816    SYooseph@jcvi.org   
Principal Investigator: Shibu Yooseph         
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Parish Sedghizadeh University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT02069340     History of Changes
Other Study ID Numbers: 0S-13-3, NCI-2014-00207, 0S-13-3, P30CA014089
Study First Received: February 7, 2014
Last Updated: February 19, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Osteonecrosis
Bisphosphonate-Associated Osteonecrosis of the Jaw
Neoplasms
Bone Diseases
Musculoskeletal Diseases
Necrosis
Pathologic Processes
Jaw Diseases
Stomatognathic Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014