Genetics in Predicting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Cancer Receiving Zoledronic Acid
9. april 2017 oppdatert av: University of Southern California
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.
Studieoversikt
Status
Tilbaketrukket
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Fase
- Ikke aktuelt
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
California
-
Los Angeles, California, Forente stater, 90033
- USC Norris Comprehensive Cancer Center
-
San Diego, California, Forente stater, 92121
- J.Craig Venter Institute-San Diego
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Diagnostisk
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Arm I (zoledronic acid over 15 minutes)
Patients receive zoledronic acid IV over 15 minutes on day 1.
|
Korrelative studier
Andre navn:
Gitt IV
Andre navn:
|
|
Eksperimentell: Arm II (zoledronic acid over 30 minutes)
Patients receive zoledronic acid IV over 30 minutes on day 1.
|
Korrelative studier
Andre navn:
Gitt IV
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Plasma concentrations of Zol collected at visits 2, 3, 4, and 5
Tidsramme: 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.
|
Up to 1 month
|
|
Urine concentrations of Zol collected at visits 2, 3, 4, and 5
Tidsramme: 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.
|
Up to 1 month
|
|
Jawbone tissue concentrations of Zol collected during surgical treatment for BRONJ
Tidsramme: 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.
|
Up to 1 month
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Identify potential risk factors for BRONJ
Tidsramme: Up to1 month
|
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.
|
Up to1 month
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Parish Sedghizadeh, University of Southern California
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Forventet)
1. juni 2016
Primær fullføring (Forventet)
1. desember 2020
Studiet fullført (Forventet)
1. juni 2021
Datoer for studieregistrering
Først innsendt
7. februar 2014
Først innsendt som oppfylte QC-kriteriene
19. februar 2014
Først lagt ut (Anslag)
24. februar 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
11. april 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. april 2017
Sist bekreftet
1. april 2017
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 0S-13-3 (Annen identifikator: USC Norris Comprehensive Cancer Center)
- P30CA014089 (U.S. NIH-stipend/kontrakt)
- NCI-2014-00207 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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