Vascular Fingerprint Validation Study

Testicular Cancer Clinical Trial

Official title:

Vascular Fingerprint to Identify Patients at Risk for Arterial Cardiovascular Events Within the First Year After Start of Cisplatin-based Chemotherapy for Testicular Cancer: a Validation Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02573584
• Other study ID #: 201500864
• Status: Completed
• Start date: October 1, 2015
• Est. completion date: April 1, 2024

Study information

• Verified date: May 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The vascular fingerprint is a simple selection tool to identify testicular cancer patients with a high risk of arterial cardiovascular events during and in the first year after cisplatin chemotherapy. Eventually, this selection method allows a relative small randomized intervention study with i.e. LMWH during chemotherapy to prove the effectiveness and safety in lowering the chance of an arterial cardiovascular event.

Description:

Since the introduction of cisplatin in the late seventies (1), the prognosis of metastatic testicular cancer patients has dramatically improved, with long-term survival rates of 80-90% (2). However, cure rates are compromised by the increased risk of cardiovascular events (3-5). Approximately 1-5% of the patients with metastatic testicular cancer develop arterial cardiovascular events during or shortly after cisplatin- and bleomycin containing chemotherapy (3-7). Arterial cardiovascular events include ischemic stroke and myocardial infarction. These arterial events are a source of serious treatment-induced morbidity and mortality as recently clearly confirmed by Fung (8). No established standard prophylaxis is available. There is an unmet need to have the possibility to identify high risk patients before start of chemotherapy in whom prophylactic anti-coagulant treatment may prevent events (9). An identification tool could maximize the benefit of an intervention without introducing too much unnecessary harm: preventive interventions also carry risk.

Recent data from the investigators' cancer center showed that before chemotherapy 22% of the metastatic cancer patients had ≥3 of the following 5 traditional cardiovascular risk factors present (high risk vascular fingerprint, figure 1): overweight, smoking, hypertension, dyslipidemia and impaired blood glucose. These patients had an increased risk to develop arterial events during or early after chemotherapy: 19% of the patients with a high risk vascular fingerprint developed an arterial cardiovascular event whereas only 2% of the patients with ≤2 risk factors developed an event . The vascular fingerprint seems an easy method to identify which metastatic testicular cancer patients are at a high risk for early arterial events and who may benefit from prophylaxis with for example low molecular weight heparins (LMWHs). To be used in the clinic these data need to be confirmed in an independent cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of metastatic TC and an indication to start with first-line cisplatin-based chemotherapy for metastatic TC

2. Classified into IGCCCG good or intermediate prognosis group

3. Younger than 50 years of age at start of chemotherapy

4. Signed informed consent

Exclusion Criteria:

1. History of previous cardiovascular disease

2. Retroperitoneal mass > 5 cm

3. Indication for anticoagulant therapy at start of chemotherapy

Related Conditions & MeSH terms

• Testicular Cancer
• Testicular Neoplasms

Locations

Country	Name	City	State
Netherlands	Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis (NKI-AVL)	Amsterdam
Netherlands	University Medical Center Groningen (UMCG)	Groningen
Netherlands	Maastricht University Medical Center (MUMC)	Maastricht
Portugal	Instituto Portuges de Oncologia Francisco Gentil (IPOLFG)	Lisbon
Switzerland	UniversitatsSpital Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Countries where clinical trial is conducted

Netherlands,  Portugal,  Switzerland, 

References & Publications (10)

DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014 Jul-Aug;64(4):252-71. doi: 10.3322/caac.21235. Epub 2014 Jun 1. — View Citation

Dieckmann KP, Gerl A, Witt J, Hartmann JT; German Testicular Cancer Study Group. Myocardial infarction and other major vascular events during chemotherapy for testicular cancer. Ann Oncol. 2010 Aug;21(8):1607-1611. doi: 10.1093/annonc/mdp597. Epub 2010 Ja — View Citation

Dieckmann KP, Struss WJ, Budde U. Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour. Anticancer Res. 2011 Dec;31(12):4501-5. — View Citation

Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977 Sep;87(3):293-8. doi: 10.7326/0003-4819-87-3-293. — View Citation

Fung C, Fossa SD, Milano MT, Sahasrabudhe DM, Peterson DR, Travis LB. Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study. J Clin Oncol. 2015 Oct 1;33(28):3105-15. doi: 10.1200/JCO.2014.60.36 — View Citation

Lubberts S, Boer H, Altena R, Meijer C, van Roon AM, Zwart N, Oosting SF, Kamphuisen PW, Nuver J, Smit AJ, Mulder AB, Lefrandt JD, Gietema JA. Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients d — View Citation

Nuver J, Smit AJ, van der Meer J, van den Berg MP, van der Graaf WT, Meinardi MT, Sleijfer DT, Hoekstra HJ, van Gessel AI, van Roon AM, Gietema JA. Acute chemotherapy-induced cardiovascular changes in patients with testicular cancer. J Clin Oncol. 2005 De — View Citation

Piketty AC, Flechon A, Laplanche A, Nouyrigat E, Droz JP, Theodore C, Fizazi K. The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area. Br J Cancer. 2005 — View Citation

Ramos JD, Yu EY. Cardiovascular Mortality in Testicular Nonseminomatous Germ Cell Tumors: Does Statistical Significance Imply Clinical Significance? J Clin Oncol. 2015 Oct 1;33(28):3075-7. doi: 10.1200/JCO.2015.62.7398. Epub 2015 Aug 24. No abstract avail — View Citation

Weijl NI, Rutten MF, Zwinderman AH, Keizer HJ, Nooy MA, Rosendaal FR, Cleton FJ, Osanto S. Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol. 2000 May;18(10):2169-78. doi: 10.1200/JCO — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of arterial cardiovascular events	Primary outcome is development of arterial cardiovascular events within the first year after start of chemotherapy. Events taken into account are: myocardial infarction (WHO ICD-10 I20-I25), ischemic cerebrovascular accidents (WHO ICD-10 I63-I66 and G45) or infarction in other specific organ systems (WHO ICD-10 K76.3, K55, D73.5, M62.2, N28.0)	first year after start of chemotherapy
Secondary	Overall survival		first year after start of chemotherapy
Secondary	Response to testicular cancer treatment (no evidence of disease / relapse / no response to treatment)		first year after start of chemotherapy
Secondary	Development of venous thromboembolic events (VTE) (WHO ICD-10 I26, I80-82)		first year after start of chemotherapy