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

Testicular Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04113122
• Other study ID #: 201700615
• Status: Recruiting
• Phase: N/A
• Start date: February 9, 2019
• Est. completion date: September 2024

Study information

• Verified date: May 2024
• Source: University Medical Center Groningen
• Contact: J. A. Gietema, prof.
• Phone: +31 50 361 2821
• Email: j.a.gietema[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

In order to be eligible to participate in the cross-sectional part of this study, a subject must meet all of the following criteria:

• 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

In order to be eligible to participate in the longitudinal part of this study, a subject must meet all of the following criteria:

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

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Not able to provide informed consent (in example in case of mental or psychiatric disability)

Related Conditions & MeSH terms

• Testicular Cancer
• Testicular Neoplasms

Intervention

Diagnostic Test:
• Skin biopsy
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
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-a), 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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	1 year
Secondary	Senescence-associated secretory phenotype (SASP)	Change in levels of the cytokines: IL-6, IL-8, VEGF	1 year
Secondary	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).	1 year
Secondary	Platinum levels	Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.	1 year
Secondary	Adipocytokines 1	Changes in levels of leptin and PAI-1 (ug/L)	1 year
Secondary	Adipocytokines 2	Changes in levels of adiponectin (ug/mL)	1 year