Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00161174
Status:
COMPLETED
Last Update Posted:
2024-05-03
First Post:
2005-09-08
Brief Title:
Cardiovascular Morbidity in Testicular Cancer Survivors Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Cardiovascular Morbidity in Testicular Cancer Survivors Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity KWF RUG 2004-3157
Status:
COMPLETED
Status Verified Date:
2024-05
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:
BACKGROUND
Evidence has emerged that patients cured with cisplatin-bleomycin chemotherapy from disseminated testicular cancer TC develop a large number of cardiovascular risk factors CRF several years later Recently we observed an increased incidence of cardiac events 10-20 years after chemotherapy possibly as a result of increased occurrence of CRF Additional cardiovascular damage was observed after treatment disturbed diastolic function of the left ventricle microalbuminuria and increased endothelial damage parameters Furthermore a metabolic syndrome syndrome X with insulin-resistance dyslipidemia hypertension and endothelial damage was found in about one third of our cured patients The investigators hypothesize that endothelial damage and metabolic changes caused by the bleomycin and cisplatin chemotherapy are the main causes for the observed increase in cardiovascular disease in these young cancer survivors Genetic susceptibility may be an important determinant of individual risk of toxicity in individual patients
PURPOSE
1 To identify risk factors for cardiovascular disease CVD following testicular cancer
2 To obtain insight into the pathways of CVD development by examining whether clinical CVD following testicular cancer is associated with a preceding unfavorable cardiovascular risk factor profile andor with treatment-related factors
3 To investigate genetic polymorphisms in pathogenetically important pathways that are potentially involved in the development of treatment related cardiovascular morbidity following testicular cancer
PATIENTS AND METHODS
Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen The Netherlands since 1977 but before 2000 are eligible 380 patients with non-seminomatous testicular cancer fulfill these criteria A close routine follow-up of these patients after treatment has been done at the University Hospital Groningen Clinical characteristics of these patients treatment details including outcome and long-term follow-up are being registered systematically From all patients who agree to participate assessment of their cardiovascular risk factors and the presence of subclinical cardiovascular damage will be performed by means of several measurement techniques Also genomic DNA will be collected for studies on polymorphisms in pathogenetically important pathways For the total cohort of patients several different late effects phenotypes of cardiovascular damage and cardiovascular risk factor patterns will be derived from the available data These toxicity phenotypes will be used to select cases and controls from the total cohort to test candidate genetic polymorphisms on their association with occurrence of toxicity The association of the different genetic polymorphisms with the toxicity phenotype will be estimated by comparing cases with different toxicity phenotypes with controls without that phenotype
POSSIBLE RESULTS This research will provide insight into the pathogenesis of cardiovascular disease after treatment for testicular cancer The main outcome will be the possibility to select individually those patients who are likely to have an increased risk to encounter specific cardiovascular toxicity during or after chemotherapy treatment for TC This will provide opportunities for the tailoring of potential toxic treatment andor guide primary and secondary prevention strategies for serious side effects of chemotherapy treatment
Evidence has emerged that patients cured with cisplatin-bleomycin chemotherapy from disseminated testicular cancer TC develop a large number of cardiovascular risk factors CRF several years later Recently we observed an increased incidence of cardiac events 10-20 years after chemotherapy possibly as a result of increased occurrence of CRF Additional cardiovascular damage was observed after treatment disturbed diastolic function of the left ventricle microalbuminuria and increased endothelial damage parameters Furthermore a metabolic syndrome syndrome X with insulin-resistance dyslipidemia hypertension and endothelial damage was found in about one third of our cured patients The investigators hypothesize that endothelial damage and metabolic changes caused by the bleomycin and cisplatin chemotherapy are the main causes for the observed increase in cardiovascular disease in these young cancer survivors Genetic susceptibility may be an important determinant of individual risk of toxicity in individual patients
PURPOSE
1 To identify risk factors for cardiovascular disease CVD following testicular cancer
2 To obtain insight into the pathways of CVD development by examining whether clinical CVD following testicular cancer is associated with a preceding unfavorable cardiovascular risk factor profile andor with treatment-related factors
3 To investigate genetic polymorphisms in pathogenetically important pathways that are potentially involved in the development of treatment related cardiovascular morbidity following testicular cancer
PATIENTS AND METHODS
Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen The Netherlands since 1977 but before 2000 are eligible 380 patients with non-seminomatous testicular cancer fulfill these criteria A close routine follow-up of these patients after treatment has been done at the University Hospital Groningen Clinical characteristics of these patients treatment details including outcome and long-term follow-up are being registered systematically From all patients who agree to participate assessment of their cardiovascular risk factors and the presence of subclinical cardiovascular damage will be performed by means of several measurement techniques Also genomic DNA will be collected for studies on polymorphisms in pathogenetically important pathways For the total cohort of patients several different late effects phenotypes of cardiovascular damage and cardiovascular risk factor patterns will be derived from the available data These toxicity phenotypes will be used to select cases and controls from the total cohort to test candidate genetic polymorphisms on their association with occurrence of toxicity The association of the different genetic polymorphisms with the toxicity phenotype will be estimated by comparing cases with different toxicity phenotypes with controls without that phenotype
POSSIBLE RESULTS This research will provide insight into the pathogenesis of cardiovascular disease after treatment for testicular cancer The main outcome will be the possibility to select individually those patients who are likely to have an increased risk to encounter specific cardiovascular toxicity during or after chemotherapy treatment for TC This will provide opportunities for the tailoring of potential toxic treatment andor guide primary and secondary prevention strategies for serious side effects of chemotherapy treatment
Detailed Description:
None
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| KWF RUG 2004-3157 | None | None | None |