TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects (TACkLE)

• ClinicalTrials.gov Identifier: NCT02276430
• Recruitment Status: Active, not recruiting
• First Posted: October 28, 2014
• Last Update Posted: June 23, 2020
• Sponsor: University Medical Center Groningen
• Collaborator: The Netherlands Cancer Institute
• Information provided by (Responsible Party): J.A. Gietema, University Medical Center Groningen

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Testicular Cancer	Other: Vena punction

Detailed 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.

Study Design

• Study Type: Observational
• Actual Enrollment: 939 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: A Case-cohort Study to Identify Risk Factors for Cardiovascular Disease in Testicular Cancer Survivors
• Study Start Date: July 2014
• Actual Primary Completion Date: May 8, 2017
• Estimated Study Completion Date: April 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cases; Patients who developed cardiovascular disease after testicular cancer treatment	Other: Vena punction; Once 90 ml
Subcohort members; A random selection out of the total cohort of testicular cancer patients per participating hospital	Other: Vena punction; Once 90 ml

Outcome Measures

Primary Outcome Measures :

1. Characteristics of disease (i.e. stage/IGCCCG prognosis group) and treatment (chemotherapy/radiotherapy) [ Time Frame: 4 years ]
   To evaluate the independent and joint effects of disease- and treatment characteristics of TC patients on cardiovascular disease risk.
2. Cardiovascular risk factors [ Time Frame: 4 years ]
   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.

Secondary Outcome Measures :

1. Biomarkers for endothelial activation, hemostatic activity and inflammatory activity after TC treatment and relation with CVD [ Time Frame: 4 years ]
   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.
2. Hypogonadism after TC treatment and relation with CVD [ Time Frame: 4 years ]
   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.
3. DNA and telomere length analysis and association with (riskfactors for) CVD [ Time Frame: 4 years ]
   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. Quality of life [ Time Frame: 4 years ]
   To investigate the impact of cardiovascular disease on Quality of Life (QoL) in TC survivors.
5. Circulating platinum levels [ Time Frame: 4 years ]
   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.
6. Intima media thickness [ Time Frame: 4 years ]
   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.
7. Arterial stiffness [ Time Frame: 4 years ]
   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.
8. Skin auto fluorescence (SAF) as measure for Advanced Glycation End products (AGEs) [ Time Frame: 4 years ]
   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.

Biospecimen Retention:   Samples With DNA

Blood samples: analysis of cardiovascular risk factors (lipid profile, glucose metabolism, hormonal status), platinum levels and several biomarkers.

Urine samples: microalbuminuria, platinum levels. DNA: polymorphisms in candidate genes for development of cardiovascular damage, leukocyte telomere length

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Testicular cancer survivors

Criteria

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

Contacts and Locations

Locations

Netherlands

Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9700 RB

University Medical Center St. Radboud

Nijmegen, Netherlands

Sponsors and Collaborators

University Medical Center Groningen

The Netherlands Cancer Institute

Investigators

• Principal Investigator: J. A. Gietema, MD, PhD; University Medical Center Groningen

More Information

• Responsible Party: J.A. Gietema, Prof.dr., University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT02276430
• Other Study ID Numbers: KWF2011-5209; NL45655.042.13 ( Other Identifier: ABR form )
• First Posted: October 28, 2014
• Last Update Posted: June 23, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by J.A. Gietema, University Medical Center Groningen:

Testicular cancer; Survivor; Cardiovascular disease; Risk factors

Additional relevant MeSH terms:

Testicular Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders