Malignant NeoplasmNCT02069340
Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
A study testing zoledronic acid and pharmacological study in people with Malignant Neoplasm and Musculoskeletal Complications, run by University of Southern California at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Malignant Neoplasm, Musculoskeletal Complications
- What is being tested?
- zoledronic acid and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2016to Jun 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
J.Craig Venter Institute-San Diego
San Diego, California, 92121
About this study
Official title: POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- Malignant Neoplasm, Musculoskeletal Complications
- Being tested
- zoledronic acid, pharmacological study
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zoledronic acidDrug
Also called CGP 42446, CGP42446A, NDC-zoledronate, zoledronate
Given IV
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (zoledronic acid over 15 minutes) | Experimental | Patients receive zoledronic acid IV over 15 minutes on day 1. Receives: Drug: zoledronic acid; Other: pharmacological study |
| Arm II (zoledronic acid over 30 minutes) | Experimental | Patients receive zoledronic acid IV over 30 minutes on day 1. Receives: Drug: zoledronic acid; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
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.
Measured: Up to 1 month
Urine concentrations of Zol collected at visits 2, 3, 4, and 5
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.
Measured: Up to 1 month
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
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.
Measured: Up to 1 month
Secondary outcomes (1)
Identify potential risk factors for BRONJ
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.
Measured: Up to1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2014 (estimated)
- Study startJun 2016 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Parish Sedghizadeh, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02069340
- Sponsor's protocol ID
- 0S-13-3
- Other IDs
- NCI-2014-00207, 0S-13-3, P30CA014089
- Status last verified
- Apr 2017
- First submitted
- 7 Feb 2014
- Last updated
- 11 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)
- ClinicalTrials.gov ID
- NCT02069340
- Acronym / sponsor ID
- 0S-13-3
- Conditions
- Malignant Neoplasm, Musculoskeletal Complications
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2016 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 24 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (zoledronic acid over 15 minutes) | Experimental | Drug: zoledronic acid, Other: pharmacological studyPatients receive zoledronic acid IV over 15 minutes on day 1. |
| Arm II (zoledronic acid over 30 minutes) | Experimental | Drug: zoledronic acid, Other: pharmacological studyPatients receive zoledronic acid IV over 30 minutes on day 1. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zoledronic acidAlso: CGP 42446, CGP42446A, NDC-zoledronate, zoledronateGiven IV | Drug | Arm I (zoledronic acid over 15 minutes), Arm II (zoledronic acid over 30 minutes) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I (zoledronic acid over 15 minutes), Arm II (zoledronic acid over 30 minutes) |
Primary outcome
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
Time frame: Up to 1 month
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
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
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.
1 secondary outcome
Identify potential risk factors for BRONJ
Time frame: Up to1 month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
Related trials for Malignant Neoplasm
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parish Sedghizadeh principal investigator
University of Southern California
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing zoledronic acid and pharmacological study in people with Malignant Neoplasm and Musculoskeletal Complications, run by University of Southern California at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5 (time frame: Up to 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2017.