Non-seminomatous Testicular CancerNCT00161174
Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity
An observational study of Non-seminomatous Testicular Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Non-seminomatous Testicular Cancer
- How many people
- 173 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2005to Jan 2011
- Phase
- Observational
- 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
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy
Who may be able to join
- 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.
Who cannot join
- N/A
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity. (KWF RUG 2004-3157)
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.
Read more
PURPOSE:
- To identify risk factors for cardiovascular disease (CVD) following testicular cancer.
- 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.
- 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.
- Conditions
- Non-seminomatous Testicular Cancer
- Keywords
- testicular cancer, cardiovascular morbidity, cardiovascular risk factors, pharmacogenomic determinants
- Medical subject headings
- Testicular Neoplasms
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startJul 2005
- Primary completionDec 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (53)Papers the sponsor has linked to this study.
- Other trials for Non-seminomatous Testicular CancerStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society
- Responsible party
- Sponsor
- Investigators
- Elisabeth G.E. de Vries, MD, PhD, Study director, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00161174
- Sponsor's protocol ID
- KWF RUG 2004-3157
- Other IDs
- KWF RUG 2004-3157
- Status last verified
- May 2024
- First submitted
- 8 Sep 2005
- Last updated
- 3 May 2024
- Results posted
- No
Publications
Einhorn LH. Treatment of testicular cancer: a new and improved model. J Clin Oncol. 1990 Nov;8(11):1777-81. doi: 10.1200/JCO.1990.8.11.1777.
PubMed 1700077Stoter G, Koopman A, Vendrik CP, Struyvenberg A, Sleyfer DT, Willemse PH, Schraffordt Koops H, van Oosterom AT, ten Bokkel Huinink WW, Pinedo HM. Ten-year survival and late sequelae in testicular cancer patients treated with cisplatin, vinblastine, and bleomycin. J Clin Oncol. 1989 Aug;7(8):1099-104. doi: 10.1200/JCO.1989.7.8.1099.
PubMed 2474060Meijer S, Sleijfer DT, Mulder NH, Sluiter WJ, Marrink J, Koops HS, Brouwers TM, Oldhoff J, van der Hem GK, Mandema E. Some effects of combination chemotherapy with cis-platinum on renal function in patients with nonseminomatous testicular carcinoma. Cancer. 1983 Jun 1;51(11):2035-40. doi: 10.1002/1097-0142(19830601)51:113.0.co;2-8.
PubMed 6340821Hansen SW, Groth S, Daugaard G, Rossing N, Rorth M. Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer. J Clin Oncol. 1988 Nov;6(11):1728-31. doi: 10.1200/JCO.1988.6.11.1728.
PubMed 2460594Roth BJ, Greist A, Kubilis PS, Williams SD, Einhorn LH. Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up. J Clin Oncol. 1988 Aug;6(8):1239-47. doi: 10.1200/JCO.1988.6.8.1239.
PubMed 2457658Vogelzang NJ, Torkelson JL, Kennedy BJ. Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin. Cancer. 1985 Dec 15;56(12):2765-70. doi: 10.1002/1097-0142(19851215)56:123.0.co;2-2.
PubMed 2413982Boyer M, Raghavan D, Harris PJ, Lietch J, Bleasel A, Walsh JC, Anderson S, Tsang CS. Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer. J Clin Oncol. 1990 Jan;8(1):21-6. doi: 10.1200/JCO.1990.8.1.21.
PubMed 1688614Doll DC, List AF, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med. 1986 Jul;105(1):48-51. doi: 10.7326/0003-4819-105-1-48.
PubMed 2424354Samuels BL, Vogelzang NJ, Kennedy BJ. Severe vascular toxicity associated with vinblastine, bleomycin, and cisplatin chemotherapy. Cancer Chemother Pharmacol. 1987;19(3):253-6. doi: 10.1007/BF00252982.
PubMed 2438065Vogelzang NJ, Frenning DH, Kennedy BJ. Coronary artery disease after treatment with bleomycin and vinblastine. Cancer Treat Rep. 1980 Oct-Nov;64(10-11):1159-60. No abstract available.
PubMed 6161700Gerl A, Clemm C, Wilmanns W. Acute cerebrovascular event after cisplatin-based chemotherapy for testicular cancer. Lancet. 1991 Aug 10;338(8763):385-6. doi: 10.1016/0140-6736(91)90521-p. No abstract available.
PubMed 1677724Nichols CR, Roth BJ, Williams SD, Gill I, Muggia FM, Stablein DM, Weiss RB, Einhorn LH. No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study. J Clin Oncol. 1992 May;10(5):760-5. doi: 10.1200/JCO.1992.10.5.760.
PubMed 1285740Gietema JA, Sleijfer DT, Willemse PH, Schraffordt Koops H, van Ittersum E, Verschuren WM, Kromhout D, Sluiter WJ, Mulder NH, de Vries EG. Long-term follow-up of cardiovascular risk factors in patients given chemotherapy for disseminated nonseminomatous testicular cancer. Ann Intern Med. 1992 May 1;116(9):709-15. doi: 10.7326/0003-4819-116-9-709.
PubMed 1558341Gietema JA, de Vries EG, Sleijfer DT. Increased incidence of cardiovascular risk factors in cured testicular cancer patients. J Clin Oncol. 1992 Oct;10(10):1652. No abstract available.
PubMed 1328550Boyer M, Raghavan D. Toxicity of treatment of germ cell tumors. Semin Oncol. 1992 Apr;19(2):128-42.
PubMed 1313191
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity. (KWF RUG 2004-3157)
- ClinicalTrials.gov ID
- NCT00161174
- Acronym / sponsor ID
- KWF RUG 2004-3157
- Conditions
- Non-seminomatous Testicular Cancer
- Keywords
- testicular cancer, cardiovascular morbidity, cardiovascular risk factors, pharmacogenomic determinants
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Dutch Cancer Society
- Study start
- Jul 2005
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 12 Sep 2005 (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.
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:
- To identify risk factors for cardiovascular disease (CVD) following testicular cancer.
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- N/A
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2024.
- Background: PubMed 1700077Einhorn LH. Treatment of testicular cancer: a new and improved model. J Clin Oncol. 1990 Nov;8(11):1777-81. doi: 10.1200/JCO.1990.8.11.1777.
- Background: PubMed 2474060Stoter G, Koopman A, Vendrik CP, Struyvenberg A, Sleyfer DT, Willemse PH, Schraffordt Koops H, van Oosterom AT, ten Bokkel Huinink WW, Pinedo HM. Ten-year survival and late sequelae in testicular cancer patients treated with cisplatin, vinblastine, and bleomycin. J Clin Oncol. 1989 Aug;7(8):1099-104. doi: 10.1200/JCO.1989.7.8.1099.
- Background: PubMed 6340821Meijer S, Sleijfer DT, Mulder NH, Sluiter WJ, Marrink J, Koops HS, Brouwers TM, Oldhoff J, van der Hem GK, Mandema E. Some effects of combination chemotherapy with cis-platinum on renal function in patients with nonseminomatous testicular carcinoma. Cancer. 1983 Jun 1;51(11):2035-40. doi: 10.1002/1097-0142(19830601)51:113.0.co;2-8.
- Background: PubMed 2460594Hansen SW, Groth S, Daugaard G, Rossing N, Rorth M. Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer. J Clin Oncol. 1988 Nov;6(11):1728-31. doi: 10.1200/JCO.1988.6.11.1728.
- Background: PubMed 2457658Roth BJ, Greist A, Kubilis PS, Williams SD, Einhorn LH. Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up. J Clin Oncol. 1988 Aug;6(8):1239-47. doi: 10.1200/JCO.1988.6.8.1239.
- Background: PubMed 2413982Vogelzang NJ, Torkelson JL, Kennedy BJ. Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin. Cancer. 1985 Dec 15;56(12):2765-70. doi: 10.1002/1097-0142(19851215)56:123.0.co;2-2.
- Background: PubMed 1688614Boyer M, Raghavan D, Harris PJ, Lietch J, Bleasel A, Walsh JC, Anderson S, Tsang CS. Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer. J Clin Oncol. 1990 Jan;8(1):21-6. doi: 10.1200/JCO.1990.8.1.21.
- Background: PubMed 2424354Doll DC, List AF, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med. 1986 Jul;105(1):48-51. doi: 10.7326/0003-4819-105-1-48.
- Background: PubMed 2438065Samuels BL, Vogelzang NJ, Kennedy BJ. Severe vascular toxicity associated with vinblastine, bleomycin, and cisplatin chemotherapy. Cancer Chemother Pharmacol. 1987;19(3):253-6. doi: 10.1007/BF00252982.
- Background: PubMed 6161700Vogelzang NJ, Frenning DH, Kennedy BJ. Coronary artery disease after treatment with bleomycin and vinblastine. Cancer Treat Rep. 1980 Oct-Nov;64(10-11):1159-60. No abstract available.
- Background: PubMed 1677724Gerl A, Clemm C, Wilmanns W. Acute cerebrovascular event after cisplatin-based chemotherapy for testicular cancer. Lancet. 1991 Aug 10;338(8763):385-6. doi: 10.1016/0140-6736(91)90521-p. No abstract available.
- Background: PubMed 1285740Nichols CR, Roth BJ, Williams SD, Gill I, Muggia FM, Stablein DM, Weiss RB, Einhorn LH. No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study. J Clin Oncol. 1992 May;10(5):760-5. doi: 10.1200/JCO.1992.10.5.760.
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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.
Elisabeth G.E. de Vries, MD, PhD study director
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-seminomatous Testicular Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
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 2 inclusion and 1 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: finished, as of the sponsor's last update on 3 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00161174, which also lists 53 linked publications.
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 3 May 2024.