Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00122265
Status:
TERMINATED
Last Update Posted:
2016-02-26
First Post:
2005-07-20
Brief Title:
Exploring Genomic Proteomic and Dosimetric Determinants of Late Toxicity After Three Dimensional Conformal Radiotherapy RT for Prostate Cancer
Sponsor:
AHS Cancer Control Alberta
Organization:
AHS Cancer Control Alberta
Study Overview
Official Title:
Exploring Genomic Proteomic and Dosimetric Determinants of Late Toxicity After Three Dimensional Conformal RT for Prostate Cancer
Status:
TERMINATED
Status Verified Date:
2012-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Prostate cancer is the most common malignancy in males and radiotherapy is a commonly chosen treatment option for patients with localized disease Technical innovations such as three-dimensional conformal radiotherapy 3D CRT and intensity-modulated radiotherapy permit radiation dose escalation and possibly better disease outcomes but escalated doses may be accompanied by long-term complications This study will examine for the first time the independent contribution of a patients own genetic makeup to the development of post-radiation complications permitting the future development of predictive tests to avoid radiation injury To do this the investigators will examine gene markers and blood proteins in a series of approximately 100 prostate cancer survivors who have received three-dimensional conformal radiotherapy between 1996 and 2000 at the Cross Cancer Institute
Detailed Description:
OBJECTIVES Major innovations in radiotherapy RT delivery 3D conformal RT intensity modulated RT now permit RT dose escalation to be tested as a means of improving control of localized prostate cancer With delivery innovations severe toxicity occurs rarely but significant bladder and rectal toxicity is common The investigators have studied a cohort of 98 patients who received dose-escalated 3D-CRT and have obtained evidence of dosimetric factors underlying rectal toxicity They posit that the late radiation toxicity disease state has significant genetic determinants These determinants are neither understood nor accounted for in selection of treatment and the investigators propose to study the above well-characterized cohort who are clinically well from a disease control perspective given that comprehensive dosimetric and outcome information is available on all
HYPOTHESIS Comprehensive analysis of the genomic proteomic and dosimetric characteristics of patients with prostate cancer will provide a novel understanding of the genetic predisposition of cellular and tissue responses to irradiation which result in the clinical occurrence of significant chronic rectal and bladder injury after 3D-CRT
APPROACH For a thorough understanding of the molecular processes underlying tissue responses to radiation damage the investigators propose a genomic analysis Their working hypothesis is that rectal and bladder toxicity will be correlated to patient genetics as measured by single nucleotide polymorphisms SNPs in a select group of genes The criteria for selecting SNPs will be based on evidence for the various genes implicated or demonstrated in DNA repair pathways and radiation-induced tissue damage In addition since radiation injury can be considered a phenotypic tissue response to RT in genetically predisposed individuals the investigators will examine the protein profile signature in sera from patients who have suffered significant toxicity Analysis of these data will be unique in that the investigators will use both statistically based bioinformatics approaches and biophysical modeling This proposal represents the most comprehensive exploration to date of the concept of a molecular signature of normal tissue radiation injury of which the applicants are aware
SPECIFIC AIM 1
To create a database of SNPs among long-term prostate cancer survivors who have been treated with 3D-CRT and for whom detailed toxicity quality of life and dosimetric information are available
To assess the feasibility of using bioinformatics approaches with this database to examine the possibility that specific SNPs in the context of known dosimetric factors can predict occurrence of late rectal or bladder toxicity
To perform a proteomic analysis of serum samples from a cohort of 25 patients experiencing higher levels of ongoing late toxicity and 50 patients with no ongoing late toxicity
SPECIFIC AIM 2
To utilize biophysical approaches to modelling clinical complication data using the concept of generalized mean biological effective dose GMBED and the critical volume model
SUMMARY This proposal will be the first comprehensive retrospective analysis of genomic proteomic and dosimetric determinants of late radiation injury in prostate cancer The investigators have assembled a broad array of expertise from the CCI PolyomX program the only high throughput SNP facility in western Canada the NCIFDA Clinical Proteomics Program at Bethesda MD and the unique biophysical modeling capability of CBIAR researchers to reach these goals
HYPOTHESIS Comprehensive analysis of the genomic proteomic and dosimetric characteristics of patients with prostate cancer will provide a novel understanding of the genetic predisposition of cellular and tissue responses to irradiation which result in the clinical occurrence of significant chronic rectal and bladder injury after 3D-CRT
APPROACH For a thorough understanding of the molecular processes underlying tissue responses to radiation damage the investigators propose a genomic analysis Their working hypothesis is that rectal and bladder toxicity will be correlated to patient genetics as measured by single nucleotide polymorphisms SNPs in a select group of genes The criteria for selecting SNPs will be based on evidence for the various genes implicated or demonstrated in DNA repair pathways and radiation-induced tissue damage In addition since radiation injury can be considered a phenotypic tissue response to RT in genetically predisposed individuals the investigators will examine the protein profile signature in sera from patients who have suffered significant toxicity Analysis of these data will be unique in that the investigators will use both statistically based bioinformatics approaches and biophysical modeling This proposal represents the most comprehensive exploration to date of the concept of a molecular signature of normal tissue radiation injury of which the applicants are aware
SPECIFIC AIM 1
To create a database of SNPs among long-term prostate cancer survivors who have been treated with 3D-CRT and for whom detailed toxicity quality of life and dosimetric information are available
To assess the feasibility of using bioinformatics approaches with this database to examine the possibility that specific SNPs in the context of known dosimetric factors can predict occurrence of late rectal or bladder toxicity
To perform a proteomic analysis of serum samples from a cohort of 25 patients experiencing higher levels of ongoing late toxicity and 50 patients with no ongoing late toxicity
SPECIFIC AIM 2
To utilize biophysical approaches to modelling clinical complication data using the concept of generalized mean biological effective dose GMBED and the critical volume model
SUMMARY This proposal will be the first comprehensive retrospective analysis of genomic proteomic and dosimetric determinants of late radiation injury in prostate cancer The investigators have assembled a broad array of expertise from the CCI PolyomX program the only high throughput SNP facility in western Canada the NCIFDA Clinical Proteomics Program at Bethesda MD and the unique biophysical modeling capability of CBIAR researchers to reach these goals
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None