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Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study

ConditionTesticular Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-50
SponsorUniversity Medical Center Groningen

About this trial

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. The investigators hypothesize that this may be an important mechanism behind development of late effects and an early ageing phenotype after treatment for testicular cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosed with metastatic testicular cancer in 1999-2012 (stage II or higher)

Received first-line cisplatin-based chemotherapy

Was younger than 50 years of age at start of chemotherapy

Diagnosis of metastatic testicular cancer (stage II or higher)

Disqualifiers

None

Trial design

Design model

Factorial

Treatments tested in this trial

  • Skin biopsy

    Diagnostic test

    A 4 mm skin biopsy will be performed at the upper leg of the patient. Before the skin biopsy local anesthesia is applied subcutaneously. In these skin biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels in the skin biopsies.

  • Subcutaneous fat biopsy

    Diagnostic test

    An abdominal subcutaneous fat biopsy will be performed 7-10 cm on the right side of the umbilicus. Before the fat biopsy local anesthesia is applied subcutaneously. An amount of 30 mg fat tissue will be collected using needle aspiration. In these fat biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels (ICP-MS), adipocytokines (leptin, adiponectin, interleukin-6, PAI-1, TNF-α), p53 activation indirectly by measuring p21 or mdm2 expression using immunohistochemistry, microRNA regulation of insulin signaling in adipose tissue: miR-103, miR-107, miR-29.

Treatment groups

192 Participants
are divided into 3 treatment groups
Group A: Cross-sectional study:Experimental treatment 2 interventions
Group B: Longitudinal study - chemotherapy groupExperimental treatment 2 interventions
Group C: Longitudinal study - stage I control groupOther 2 interventions

Trial outcomes

Primary outcomes

1

Cellular senescence

The change in the amount of senescent cells in skin and fat tissue (defined as % of cells in which nucleus is stained positive for P16, P21 and yH2Ax)

Time frame
1 year

Secondary outcomes

1

Senescence-associated secretory phenotype (SASP)

Change in levels of the cytokines: IL-6, IL-8, VEGF

Time frame
1 year
2

Pulse-wave velocity

Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV).

Time frame
1 year
3

Platinum levels

Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.

Time frame
1 year
4

Adipocytokines 1

Changes in levels of leptin and PAI-1 (ug/L)

Time frame
1 year

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Medical Center Groningen

Lead sponsor

Dutch Cancer Society

Collaborator

Source ClinicalTrials.gov
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