Diagnostic and Prognostic Value of Liquid Biopsy in Germ Cell Tumors
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 主要终点
- Percentage of patients with detectable ctDNA
研究概览
简要总结
Theoretical framework: Testicular germ cell tumors (TGCT) are characterized by frequent chromosomal anomalies such as gain of chromosome 12p and low rates of somatic mutations. Cell-free circulating tumor DNA (ctDNA) has been investigated in some cancers but only a few studies explored the presence of ctDNA in TGCT. The consistent gain of genetic material from chromosome 12p makes TGCT patients to ideal candidates for liquid biopsy investigations. We have analyzed three pre-chemo samples with our plasma-Seq approach and applied the ichorCNA algorithm to call for somatic copy number alterations (SCNA) and estimate the tumor fraction. Besides the frequently observed chromosome 12p gain, a variety of other SCNA were detected indicating that shallow whole genome sequencing (sWGS) is a suitable approach to analyze ctDNA in TGCT. Only 60% of TGCT patients express the classical markers alpha fetoprotein (AFP) and beta (human chorionic gonadotropin) HCG. Biomarkers to monitor patients who don't express the classical markers are of great need.
Hypotheses: We postulate that tumor-specific aberrations can be detected non-invasively in plasma DNA from patients with metastatic TGCT and serve as a diagnostic tool. Furthermore, we will investigate if the change of ctDNA during curative treatment can be used as monitoring tool and allows risk classification in comparison to conventional markers and the novel micro RNA biomarker miR-371a-3p (prognostic value of ctDNA).
Methods: For ctDNA and micro RNA analysis, blood samples will be drawn from patients before orchiectomy, before chemotherapy start, prior to the second cycle of chemotherapy, after completion of treatment and in case of relapse. In order to identify SCNA and to estimate the tumor content in plasma we will employ sWGS and analyze the data with the ichorCNA algorithm for a detection of SCNA. Since TGCT have low rates of somatic mutations, orchiectomy samples from patients with disease recurrence and plasma samples at time of recurrence will also be compared with the Biomodal platform which allows analysis of genetic as well as epigenetic changes.
详细描述
Study design This is a prospective, non-therapeutic trial to test the diagnostic and prognostic value of ctDNA in TGCT patients. 100 patients with metastatic TGCT presenting to treating centers in Austria, centers from the SAG registry and selected centers from Germany will be asked to participate and blood will be drawn for ctDNA and miR-371a-3p analysis during the course of disease at defined time points. In addition, 100 patients with stage I disease within Austria will be included.
Sampling Prior to surgery and intraoperative: Plasma and micro RNA samples will also be obtained prior to surgery. Plasma will be also obtained intraoperatively form the testicular vein.
After orchiectomy (before the 1st cycle of chemotherapy): Blood will be drawn into two PAXgene® Blood ccfDNA tubes (approx. 20ml) for ctDNA analysis before the start of chemotherapy. PAXgene tubes and tumor tissue will be send and stored at the Biobank of the Medical University of Graz. For the miR-371a-3p collection 10ml blood will be collected in serum tubes, centrifuged and 2ml serum stored at -80°.
Before the second cycle of chemotherapy: To evaluate treatment response with ctDNA levels, two PAXgene® Blood ccfDNA tubes (approx. 20ml) will be collected before the application of the second chemotherapy cycle. For the miR-371a-3p collection 10ml blood will be collected and processed as described above.
After completion of treatment: When the patient has completed first line treatment another two PAXgene® Blood ccfDNA tubes (approx. 20ml) will be drawn for ctDNA analysis. For the miR-371a-3p collection 10ml blood will be collected and processed as described above.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients with the age ≥ 18years with
- •Seminomatous or non-seminomatous germ cell tumors (extragonadal origin is allowed)
- •Metastatic disease
- •Stage I patients on active surveillance (for seminoma patients at least one risk factor, rete testis infiltration or tumor size > 4cm, should be present)
排除标准
- •Other tumors than germ cell tumors of the testis
- •Patients with a second malignancy within the last 5 years (except germ cell tumors)
- •Stage I patients who received adjuvant treatment
研究组 & 干预措施
Stage I
non-metastatic testicular germ cell tumors
Stage II-III
metastatic testicular germ cell tumors
结局指标
主要结局
Percentage of patients with detectable ctDNA
时间窗: 2 years
次要结局
- To compare the sensitivity and specificity of ctDNA with miR-371a-3p(2 years)