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

Обзор

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.

Вмешательства

• Диагностический тест 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.
• Диагностический тест 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 e

Первичные конечные точки

• Cellular senescence [Срок оценки: 1 year]

Вторичные конечные точки (5)

• Senescence-associated secretory phenotype (SASP) [Срок оценки: 1 year]
• Pulse-wave velocity [Срок оценки: 1 year]
• Platinum levels [Срок оценки: 1 year]
• Adipocytokines 1 [Срок оценки: 1 year]
• Adipocytokines 2 [Срок оценки: 1 year]

Критерии участия

Критерии включения

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

Критерии исключения

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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Нидерланды · 1 центр

• University Medical Center Groningen — Groningen

Идентификаторы

NCT: NCT04113122 · 201700615

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗