Genetic Risk of Osteonecrosis of the Jaw (ONJ) in Patients With Metastatic Cancer

This study seeks to identify risk factors associated with the development of a jaw condition seen in patients with cancer treated with certain medications.

Study Overview

• Status: Completed
• Conditions: Bone Diseases; Osteonecrosis; Metastases; Bisphosphonate-Associated Osteonecrosis of the Jaw

Detailed Description

The goal of this research is to build an index of risk for estimating an individual's risk of developing osteonecrosis of the jaw (ONJ). The bisphosphonates are an important supportive therapy in the care of patients with metastatic bone disease; they are able to prevent catastrophic events such as fracture and spinal cord compression. However, ONJ has been associated with the use of the bisphosphonates and ONJ carries significant morbidity. Presently, there are insufficient data to calculate the ONJ risk benefit ratio of bisphosphonate use. An ONJ risk assessment tool would improve both the oncologist's and the dental health professional the ability to anticipate and potentially mitigate oral toxicities from bisphosphonate therapy.

This protocol consists of a case (ONJ) control (no ONJ) study to identify factors associated with the risk of ONJ and to build an index predictive of an individual's risk of developing ONJ. The index of ONJ risk will be comprised of clinical, epidemiologic and genetic factors

• Study Type: Observational
• Enrollment (Actual): 271

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Academic medical center(s)

Description

Inclusion Criteria:

• The study candidate must have sufficient Formalin Fixed Paraffin Embedded (FFPE)Specimens (lymph node or tumor) for DNA extraction available for study SNP assessment
• Patients over the age of 21 with a histologically confirmed diagnosis of cancer who have received nitrogen containing bisphosphonate therapy for metastatic bone disease.
• FFPE tissues are to have been removed for clinical indication and sufficience study volume of specimen must be available in an established tissue repository.

• - Study FFPE tissues include:

  • formalin fixed paraffin embedded leukocytes from lymph nodes with or without involvement by tumor AND/OR
  • formalin fixed paraffin embedded tumor tissue (tumor block without invasive cancer is acceptable if the specimen is believed to be sufficiently cellular (breast tissue or noninvasive cancer) to yield adequate DNA)
• Medical records available for data abstraction

Exclusion Criteria:

• Insufficient specimen available to perform the assays proposed for specimen DNA analysis
• No accessable medical records

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ONJ; Patient with cancer involving the bone treated with osteoclast inhibitor (bisphosphonate) and has developed ONJ
No ONJ; Patient with cancer involving the bone treated with osteoclast inhibitor (bisphosphonate) and has NOT developed ONJ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify clinical and epidemiologic characteristics associated with ONJ in patients with metastatic bone disease treated with a nitrogen containing bisphosphonate.	analysis is ongoing	2009-2014
To identify single nucleotide polymorphisms (SNPs) in genes affected by osteoclast inhibiting therapy that are associated with an increased risk of developing ONJ in patients with metastatic bone disease treated with nitrogen containing bisphosphonates.	analysis is ongoing	2009-2014
To generate a multifactorial index of ONJ risk by multivariate analysis of the clinical, epidemiologic and genetic factors	analysis is ongoing	2009-2014

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: M.D. Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; National Institute of Dental and Craniofacial Research (NIDCR); Indiana University
• Investigators: Principal Investigator: Catherine Van Poznak, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Osteonecrosis of the Jaw (ONJ)
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Neoplasms; Musculoskeletal Diseases; Stomatognathic Diseases; Neoplastic Processes; Jaw Diseases; Neoplasm Metastasis; Bone Diseases; Osteonecrosis; Bisphosphonate-Associated Osteonecrosis of the Jaw
• Other Study ID Numbers: HUM00040101; 5K23DE020197-02 (U.S. NIH Grant/Contract)