TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects

Testicular Cancer Clinical Trial

— TACkLE  

Official title:

A Case-cohort Study to Identify Risk Factors for Cardiovascular Disease in Testicular Cancer Survivors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02276430
• Other study ID #: KWF2011-5209
• Secondary ID: NL45655.042.13
• Status: Active, not recruiting
• Start date: July 2014
• Est. completion date: April 2025

Study information

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

Clinical Trial Summary

Testicular cancer (TC) is a rare disease, which mostly affects young men aged 15-35 years. Their life expectancy has greatly improved due to the introduction of platinum-containing chemotherapy for disseminated TC in the late 1970s. Given the good prognosis of TC nowadays, prevention or early detection of late adverse effects of TC treatment has become increasingly important. Current literature suggests that TC treatment, and specifically exposure to platinum agents, is associated with increased risk of cardiovascular morbidity and mortality. The precise role of treatment components like platinum in the pathogenesis of cardiometabolic changes and cardiovascular disease (CVD) warrants further investigation, since it is not known if CVD develops through direct platinum-induced damage of the vascular wall or by mediation through development of cardiometabolic riskfactors. The aim of this study is to identify risk factors for development for CVD after treatment for TC. A more profound insight into pathophysiologic mechanisms and identification of risk factors for CVDs is needed to facilitate development of preventive strategies and to optimize survivorship care.

Description:

Design: The investigators will perform a multicenter case-cohort study. Patients treated for TC who developed cardiac disease ((either myocardial infarction, proven coronary artery disease (grade ≥2) or congestive heart failure (grade ≥2)) will be invited by their (former) treating oncologist to participate in this study (cases). Furthermore, in each hospital a random sample of 15% of the total population treated for TC will be invited (the subcohort). The investigators will collect detailed diagnostic- and treatment data on TC and on (risk factors for) CVD for all cases as well as for all subcohort members. All cases and subcohort members will be approached to complete a questionnaire and to donate a blood sample for DNA analysis, after written informed consent. Patients who were younger than 40 years at TC diagnosis and younger than 75 years at moment of study contact will be asked to participate in the cardiometabolic risk inventory sub study. For this, participants have to undergo a basic study assessment consisting of physical examination, venapuncture and handing in a morning urine sample. This assessment can be performed at the participating hospital, their general practitioner or during a home visit by a member of the investigators research team. Additional (non-invasive) cardiovascular function measurements (IMT and AGEs) are only performed in the UMCG.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 939
• Est. completion date: April 2025
• Est. primary completion date: May 8, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

All participating patients have to meet the following criteria:

• Alive
• TC diagnosis between 01-01-1976 to 31-12-2007
• TC treatment center: UMCG, NKI/AVL, Erasmus MC, UMCN, LUMC
• Younger than 50 years of age at TC diagnosis
• Written informed consent

Cases have to fulfill, beside the aforementioned criteria, the following criteria:

• Diagnosed with either myocardial infarction (MI), proven coronary artery disease (CAD) (CTCAE-4 grade 2 or higher) or congestive heart failure (CHF) (CTCAE-4 grade 2 or higher).
• No medical history of CVD before diagnosis of TC In order to be eligible to participate in the cardiometabolic risk inventory study (and to be invited to a study assessment), a subject must meet, next to the criteria mentioned in

"1)", the following inclusion criteria:

• Younger than 40 years of age at TC diagnosis
• Younger than 75 years of age at moment of inclusion Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from

participation in this study:

• Mental disorder (no informed consent available)
• Presence of active malignant disease

Related Conditions & MeSH terms

• Testicular Cancer
• Testicular Neoplasms

Intervention

Other:
• Vena punction
Once 90 ml

Locations

Country	Name	City	State
Netherlands	Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	University Medical Center St. Radboud	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characteristics of disease (i.e. stage/IGCCCG prognosis group) and treatment (chemotherapy/radiotherapy)	To evaluate the independent and joint effects of disease- and treatment characteristics of TC patients on cardiovascular disease risk.	4 years
Primary	Cardiovascular risk factors	To evaluate the effect of cardiometabolic risk factors (presence of metabolic syndrome, smoking behaviour, obesity, hypertension, dyslipidemia, diabetes mellitus, family history, physical activity) on cardiovascular disease risk in TC patients.	4 years
Secondary	Biomarkers for endothelial activation, hemostatic activity and inflammatory activity after TC treatment and relation with CVD	To determine endothelial activation, hemostatic activity and inflammatory activity (represented by circulating biochemical markers) years after treatment for TC and its relationship between development of (components of) the metabolic syndrome and development of cardiovascular diseases.	4 years
Secondary	Hypogonadism after TC treatment and relation with CVD	To evaluate the presence of hypogonadism in TC survivors and to investigate the association between hypogonadism and presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years
Secondary	DNA and telomere length analysis and association with (riskfactors for) CVD	To investigate the presence of candidate single nucleotide polymorphisms in genomic DNA and telomere length and its association with presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years
Secondary	Quality of life	To investigate the impact of cardiovascular disease on Quality of Life (QoL) in TC survivors.	4 years
Secondary	Circulating platinum levels	In patients treated with platinum-containing chemotherapy: to evaluate circulating platinum levels in TC survivors and to investigate the relationship between circulating platinum levels and presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years
Secondary	Intima media thickness	Patients visiting the UMCG for the study visit: to evaluate thickness of the intima media of the carotid artery as a marker for subclinical damage in TC survivors, and to investigate the relationship between abnormal intima media thickness and presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years
Secondary	Arterial stiffness	Patients visiting the UMCG for the study visit: to assess the elasticity of the arterial wall of the carotid artery in TC survivors, and to investigate the relationship between abnormal arterial stiffness and presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years
Secondary	Skin auto fluorescence (SAF) as measure for Advanced Glycation End products (AGEs)	Patients visiting the UMCG for the study visit: to assess levels of AGEs with help of the SAF in TC survivors and to to investigate the relationship between SAF and presence of (components of) the metabolic syndrome and development of cardiovascular disease.	4 years