Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
- Conditions
- Testicular Cancer
- Interventions
- Diagnostic Test: Skin biopsyDiagnostic Test: Subcutaneous fat biopsy
- Registration Number
- NCT04113122
- Lead Sponsor
- University Medical Center Groningen
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 192
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
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Longitudinal study - chemotherapy group Subcutaneous fat biopsy 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 Cross-sectional study: Subcutaneous fat biopsy 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. Cross-sectional study: Skin biopsy 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. Longitudinal study - stage I control group Subcutaneous fat biopsy Patients with stage I testicular cancer will serve as control group with three study visits: Visit 1: at time of orchidectomy Visit 2: one month Visit 3: one year after orchidectomy Longitudinal study - chemotherapy group Skin biopsy 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 Longitudinal study - stage I control group Skin biopsy Patients with stage I testicular cancer will serve as control group with three study visits: Visit 1: at time of orchidectomy Visit 2: one month Visit 3: one year after orchidectomy
- Primary Outcome Measures
Name Time Method Cellular senescence 1 year 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)
- Secondary Outcome Measures
Name Time Method Senescence-associated secretory phenotype (SASP) 1 year Change in levels of the cytokines: IL-6, IL-8, VEGF
Pulse-wave velocity 1 year Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV).
Adipocytokines 2 1 year Changes in levels of adiponectin (ug/mL)
Platinum levels 1 year Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.
Adipocytokines 1 1 year Changes in levels of leptin and PAI-1 (ug/L)
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands
University Medical Center Groningen🇳🇱Groningen, NetherlandsJ. A. Gietema, Prof.Principal Investigator