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

Primary Purpose

Testicular Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Skin biopsy
Subcutaneous fat biopsy
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Testicular Cancer

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

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)

Sites / Locations

  • University Medical Center GroningenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

Cross-sectional study:

Longitudinal study - chemotherapy group

Longitudinal study - stage I control group

Arm Description

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.

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

First Posted
January 8, 2019
Last Updated
January 3, 2023
Sponsor
University Medical Center Groningen
Collaborators
Dutch Cancer Society
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1. Study Identification

Unique Protocol Identification Number
NCT04113122
Brief Title
Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
Official Title
Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 9, 2019 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Dutch Cancer Society

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Testicular Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
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)
Allocation
Non-Randomized
Enrollment
192 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cross-sectional study:
Arm Type
Experimental
Arm Description
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.
Arm Title
Longitudinal study - chemotherapy group
Arm Type
Experimental
Arm Description
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
Arm Title
Longitudinal study - stage I control group
Arm Type
Other
Arm Description
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
Intervention Type
Diagnostic Test
Intervention Name(s)
Skin biopsy
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Subcutaneous fat biopsy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cellular senescence
Description
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 Outcome Measure Information:
Title
Senescence-associated secretory phenotype (SASP)
Description
Change in levels of the cytokines: IL-6, IL-8, VEGF
Time Frame
1 year
Title
Pulse-wave velocity
Description
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
Title
Platinum levels
Description
Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.
Time Frame
1 year
Title
Adipocytokines 1
Description
Changes in levels of leptin and PAI-1 (ug/L)
Time Frame
1 year
Title
Adipocytokines 2
Description
Changes in levels of adiponectin (ug/mL)
Time Frame
1 year

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
J. A. Gietema, prof.
Phone
+31 50 361 2821
Email
j.a.gietema@umcg.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. A. Gietema, Prof.
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J. A. Gietema, Prof.
Phone
+31 50 361 2821
Email
j.a.gietema@umcg.nl
First Name & Middle Initial & Last Name & Degree
J. A. Gietema, Prof.

12. IPD Sharing Statement

Learn more about this trial

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

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