Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University Medical Centre Groningen.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by:
University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00161174
First received: September 8, 2005
Last updated: February 24, 2009
Last verified: February 2009
  Purpose

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 pathway(s) of CVD development, by examining whether clinical CVD following testicular cancer is associated with a preceding unfavorable cardiovascular risk factor profile and/or 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 and/or guide primary and secondary prevention strategies for serious side effects of chemotherapy treatment.


Condition
Non-Seminomatous Testicular Cancer

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity. (KWF RUG 2004-3157)

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Estimated Enrollment: 310
Study Start Date: July 2005
Estimated Study Completion Date: December 2010
  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with non-seminomatous testicular cancer
  • Have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen, The Netherlands, since 1977 but before 01-01-2000 are eligible.

Exclusion Criteria:

  • N/A
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00161174

Contacts
Contact: Jourik A. Gietema, MD, PhD +31 50 361 2821 j.a.gietema@int.umcg.nl
Contact: Esther C. de Haas, MD +31 50 361 1645 e.c.de.haas@int.umcg.nl

Locations
Netherlands
University Medical Centre Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Jourik A. Gietema, MD, PhD    +31 50 361 1334    j.a.gietema@int.umcg.nl   
Contact: Esther C. de Haas, MD    +31 50 361 1645    e.c.de.haas@int.umcg.nl   
Sponsors and Collaborators
University Medical Centre Groningen
Dutch Cancer Society
Investigators
Study Director: Elisabeth G.E. de Vries, MD, PhD University Medical Centre Groningen
  More Information

Publications:
Meinardi MT, Gietema JA, Van der Graaf WTA et al. Long-term vascular and metabolic sequelae of chemotherapy for metastatic testicular cancer. A comparison with long-term survivors of stage I disease. PROC ASCO 2000; 19: 331a.

ClinicalTrials.gov Identifier: NCT00161174     History of Changes
Other Study ID Numbers: KWF RUG 2004-3157, KWF RUG 2004-3157
Study First Received: September 8, 2005
Last Updated: February 24, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
testicular cancer
cardiovascular morbidity
cardiovascular risk factors
pharmacogenomic determinants

Additional relevant MeSH terms:
Testicular Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on September 18, 2014