Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
1 other identifier
interventional
192
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2019
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 8, 2019
CompletedStudy Start
First participant enrolled
February 9, 2019
CompletedFirst Posted
Study publicly available on registry
October 2, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2026
December 13, 2024
November 1, 2024
7.6 years
January 8, 2019
December 9, 2024
Conditions
Outcome Measures
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)
1 year
Secondary Outcomes (5)
Senescence-associated secretory phenotype (SASP)
1 year
Pulse-wave velocity
1 year
Platinum levels
1 year
Adipocytokines 1
1 year
Adipocytokines 2
1 year
Study Arms (3)
Cross-sectional study:
EXPERIMENTALTesticular 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 - chemotherapy group
EXPERIMENTALPatients 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
OTHERPatients 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
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Medical Center Groningenlead
- Dutch Cancer Societycollaborator
Study Sites (1)
University Medical Center Groningen
Groningen, 9713 GZ, Netherlands
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
J. A. Gietema, Prof.
University Medical Center Groningen
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 8, 2019
First Posted
October 2, 2019
Study Start
February 9, 2019
Primary Completion (Estimated)
September 1, 2026
Study Completion (Estimated)
September 1, 2026
Last Updated
December 13, 2024
Record last verified: 2024-11