The aim of this study is to improve our understanding of the development of late effects after cancer treatment and reveal potential targets for intervention/prevention. Therefore we will investigate mechanisms behind the early ageing phenotype…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In the cross-sectional part of this study the primary endpoint is correlation
between senescence and the early ageing phenotype. The amount of senescent
cells in skin and fat tissue will be correlated with the early ageing phenotype
defined as
a) vascular stiffness (pulse wave velocity, PWV), the gold standard measurement
for vascular age and
b) the metabolic syndrome.
In the longitudinal part of the study the primary endpoint will be to
investigate the development of senescent burden during cisplatin-combination
chemotherapy. The percentage, and -if any- upregulation of senescent cells in
skin and fat tissue will be measured and compared between pre-chemotherapy
measurements and the different time points afterwards and compared between the
chemotherapy group, the stage I control group and the healthy control group.
Secondary outcome
- Senescence-associated secretory phenotype (SASP): Defined as elevated levels
of the cytokines IL-6, IL-8 or VEGF.
- (Sub)clinical features of the early ageing phenotype: Presence or development
of the early ageing phenotype will be assessed measuring vascular damage
(vascular stiffness (pulse-wave velocity, PWV), biomarkers, intima-media
thickness (IMT), peripheral digital ischaemia, systolic and diastolic cardiac
function, global longitudinal strain (GLS), and advanced glycation end products
(AGEs) as measure for metabolic memory). Presence or development of
cardiovascular risk factors will be assessed (body mass index, waist-hip ratio,
blood pressure, lipid profile, fasting glucose and presence of the metabolic
syndrome.
- Platinum levels: Both circulating platinum levels and the amount of platinum
depositions in skin and fat tissue will be assessed (ICP-MS).
- Fat tissue metabolism and metabolic state: The adipocytokines (leptin,
adiponectin, IL-6, PAI-1, TNF-α), p53 activation and microRNA regulation of
insulin signaling in adipose tissue: miR-103, miR-107, miR-29) will be
measured.
Background summary
Cisplatin-combination chemotherapy causes inevitably DNA damage by platinum-DNA
adduct formation of both tumor cells but also healthy cells. It therefore
stands to reason that testicular cancer treatment causes an increased burden of
senescent cells, which causes upregulation of the SASP resulting in a
pro-inflammatory phenotype. We hypothesize that this may be an important
mechanism behind development of late effects and an early ageing phenotype
after treatment for testicular cancer.
Study objective
The aim of this study is to improve our understanding of the development of
late effects after cancer treatment and reveal potential targets for
intervention/prevention. Therefore we will investigate mechanisms behind the
early ageing phenotype emerging after cisplatin-combination treatment for
testicular cancer.
Study design
A study will be performed consisting of a cross-sectional part and a
longitudinal part with two cohorts.
Cross-sectional study:
1. Testicular cancer survivors who were treated between 2000 and 2005 or
between 2006 and 2012 with cisplatin-combination chemotherapy and who were
extensively phenotypically mapped within two longitudinal trials (15,16) will
be invited to participate in a single cross-sectional follow-up study visit
5-20 years after chemotherapy.
2. Testicular cancer survivors who were treated between 2013 and 2019 with
cisplatin-combination chemotherapy and who were extensively phenotypically
mapped within the ACT trial, (Optimal Timing of a Tailored Physical Activity
Program During Chemotherapeutic Cancer Treatment to Reduce Long-term
Cardiovascular Morbidity; clinicaltrails.gov: NCT01642680), will also be
invited to participate in a single cross-sectional follow-up study visit 1.5-10
years after chemotherapy.
*
Longitudinal study:
Patients with metastasized testicular cancer who are about to start with
cisplatin-combination chemotherapy will be invited in the longitudinal part of
this study. Study participation involves four study visits:
Visit 1: before start of chemotherapy
Visit 2: before third cycle of chemotherapy
Visit 3: one month after completion of chemotherapy
Visit 4: one year after start of chemotherapy
Patients with stage I testicular cancer will serve as control group with two
study visits:
Visit 1:one to two months after orchidectomy
Visit 2: one year after orchidectomy.
Healthy male volunteers who were not treated for any type of cancer will serve
as a second control group. Study participation involves one study visit.
Study burden and risks
In case of participation in the cross-sectional part of this study one visit
during one morning will be planned. In case of participation in the
longitudinal part of this study four (chemotherapy-group) or two (stage I
control-group) visits , or one visit (healthy control-group) during one morning
per visit will be planned. Invasive procedures are the skin and fat biopsy and
a venapuncture. All three procedures have a low risk of adverse effects.
Hanzeplein 1
GRONINGEN 9713 GZ
NL
Hanzeplein 1
GRONINGEN 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
Cross-sectional part of this study:
- Diagnosed with metastatic testicular cancer in 1999-2019 and participated in
the above mentioned longitudinal studies (stage II or higher)
- Received first-line cisplatin-based chemotherapy
- Was younger than 50 years of age at start of chemotherapy, Longitudinal part
of this study:
Chemotherapy-group:
- Diagnosis of metastatic testicular cancer (stage II or higher)
- Is about to start with first-line cisplatin-based chemotherapy
- Younger than 50 years of age at diagnosis of metastatic testicular cancer,
Stage I control-group:
- Diagnosis of testicular cancer stage I disease
- Younger than 50 years of age at diagnosis of testicular cancer
In order to be eligible to participate in the control group of this study, a
subject must meet all of the following criteria:
Healthy control-group:
- Male younger than 60 years of age
Exclusion criteria
- Earlier diagnosis with another malignancy except from successfully treated
squamous cell carcinoma of the skin.
- Not able to provide informed consent (in example in case of mental or
psychiatric disability)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04113122 |
| CCMO | NL63331.042.17 |