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

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ClinicalTrials.gov Identifier: NCT04113122
Recruitment Status : Recruiting
First Posted : October 2, 2019
Last Update Posted : February 2, 2021
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by (Responsible Party):
J.A. Gietema, University Medical Center Groningen

Tracking Information
First Submitted Date  ICMJE January 8, 2019
First Posted Date  ICMJE October 2, 2019
Last Update Posted Date February 2, 2021
Actual Study Start Date  ICMJE February 9, 2019
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
Cellular senescence [ Time Frame: 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2019)
  • Senescence-associated secretory phenotype (SASP) [ Time Frame: 1 year ]
    Change in levels of the cytokines: IL-6, IL-8, VEGF
  • Pulse-wave velocity [ Time Frame: 1 year ]
    Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV).
  • Platinum levels [ Time Frame: 1 year ]
    Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.
  • Adipocytokines 1 [ Time Frame: 1 year ]
    Changes in levels of leptin and PAI-1 (ug/L)
  • Adipocytokines 2 [ Time Frame: 1 year ]
    Changes in levels of adiponectin (ug/mL)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Senescence-associated secretory phenotype (SASP) [ Time Frame: 1 year ]
    Change in levels of the cytokines: IL-6, IL-8, VEGF
  • (Sub) clinical features of the early ageing phenotype [ Time Frame: 1 year ]
    Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV).
  • Platinum levels [ Time Frame: 1 year ]
    Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.
  • Fat tissue metabolism and metabolic state [ Time Frame: 1 year ]
    Changes in levels of adipocytokines.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
Official Title  ICMJE Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:

A study will be performed consisting of two cohorts. Cross-sectional study Testicular cancer survivors treated between 2000 and 2005 or between 2006 and 2012 with cisplatin-combination chemotherapy and were extensively phenotypically mapped within two longitudinal trials will be invited to participate in a single cross-sectional follow-up study visit 5-20 years after chemotherapy.

Longitudinal study

Patients with metastasized testicular cancer who are about to start with cisplatin-combination chemotherapy will be invited. 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 three study visits:

Visit 1: at time of orchidectomy Visit 2: one month after orchidectomy Visit 3: one year after orchidectomy

Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Testicular Cancer
Intervention  ICMJE
  • 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.
  • Diagnostic Test: 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-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.

Study Arms  ICMJE
  • Experimental: Cross-sectional study:
    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.
    Interventions:
    • Diagnostic Test: Skin biopsy
    • Diagnostic Test: Subcutaneous fat biopsy
  • Experimental: Longitudinal study - chemotherapy group

    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

    Interventions:
    • Diagnostic Test: Skin biopsy
    • Diagnostic Test: Subcutaneous fat biopsy
  • Longitudinal study - stage I control group

    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

    Interventions:
    • Diagnostic Test: Skin biopsy
    • Diagnostic Test: Subcutaneous fat biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 1, 2019)
192
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: J. A. Gietema, prof. +31 50 361 2821 j.a.gietema@umcg.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04113122
Other Study ID Numbers  ICMJE 201700615
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party J.A. Gietema, University Medical Center Groningen
Study Sponsor  ICMJE University Medical Center Groningen
Collaborators  ICMJE Dutch Cancer Society
Investigators  ICMJE
Principal Investigator: J. A. Gietema, Prof. University Medical Center Groningen
PRS Account University Medical Center Groningen
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP