A Platform for Assessing Personal Risk of Developing or Recurring of Cancer: Study of Biological, Genetic, and Constitutional Factors and Non-invasive Monitoring of Subclinical Recurrences With Therapeutic Impact
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 850
- 试验地点
- 1
- 主要终点
- Number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
研究概览
简要总结
The PRO-ACTIVE study aims to develop a clinical-translational program in the field of cancer prevention in all its phases (primary, secondary, and tertiary) to intervene before the clinical and radiological manifestation of the disease. It starts with risk prediction and leads to early diagnosis of the disease or recurrence in the subclinical phase.
The PRO-ACTIVE study includes the following activities:
- WP1: Integrated DNA-RNA approach for the identification of hereditary markers of predisposition to tumors
- WP2: Global biological and molecular analysis of the host and tumor for the prevention and monitoring of recurrences
- WP3: Analysis of the immunological status for the diagnosis of primary prevention and relapses in correlation to genetic and environmental factors
- WP4: Study of the tumor microenvironment for recurrence prediction
详细描述
The observational study consists of a retrospective and a prospective part.
For the retrospective part 400 patients with breast tumors operated between 2000 and 2015 will be selected, of which 200 with hereditary breast tumors and 200 with non-hereditary breast tumors and with the following clinical, morphological and molecular class characteristics (luminal A and B, triple negatives) and stackable staging.
The tumor tissue will be subjected to immunocytochemical investigations to study the following parameters: angiogenesis (CD31), fibroblasts (CD34 and vimentin), macrophages (CD68) and tumor associated macrophages (M1: CD11c; M2: CD163); plasma cells (CD138), T lymphocytes (CD8); Mast cells (CD117).
The data will be correlated with the prognosis and with the risk of developing hereditary breast cancer.
The prospective part, on the other hand, envisages the enrollment of different cohorts of patients who are initially screened in WP1.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years;
- •Patients with breast cancer, including patients who meet the AIOM criteria for eligibility for BRCA testing and patients with lobular breast cancer;
- •Patients with radically resected colon cancer, including patients with stage III colon cancer and vascular invasion;
- •Patients with ovarian carcinomas;
- •Patients with metastatic melanoma;
- •Patients with stage IIB and IIIA non-small cell lung cancer.
排除标准
- •Age <18 years;
- •Unwillingness or inability to give informed consent
研究组 & 干预措施
Cohort 1
600 patients known for breast cancer (N=200), ovarian cancer (N=200) and colorectal cancer (N=200) candidates for germline genetic testing in the context of an oncogenic consultation will be evaluated.
Cohort 2A
Subjects with hereditary inheritance (probands): the identification of about 10% (N=60) of probands out of 600 subjects examined (20 for pathology) is assumed
Cohort 2B
Subjects identified by genetic counseling as being at risk of being carriers of a hereditary neoplastic syndrome, not proven by genetic tests: a population of 60 subjects, 20 for each type of tumour, with similar clinical characteristics of age and phenotype compared to cohort 2A.
Cohort 2C
50 subjects for each type of tumor (colorectal, breast and ovarian cancer), negative results in diagnostic genetic analysis. In selected patients in this cohort, DNA/RNA will be analyzed for the identification of causative genetic variants in genes that have escaped routine diagnostic investigation.
Cohort 3
250 patients undergoing radical surgical treatment and with the following characteristics:
- locally advanced breast cancer with triple negative phenotype or with lobular histology (N=50);
- high-grade serous ovarian carcinoma (N=50);
- stage III melanoma (N=50);
- stage IIB and IIIA non-small cell lung cancer (N=50);
- colon cancer with lymph node involvement and vascular invasion (N=50).
结局指标
主要结局
Number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
时间窗: From enrollment to the last clinical follow-up at month 12
Patients will undergo blood sampling for the extraction of nucleic acids (DNA and RNA) to determine number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
次要结局
- Number of isolated circulating tumour cells (CTCs) in patients' blood(From enrollment to the last clinical follow-up at month 12)
- Amount of circulating tumour DNA (ctDNA) in patients' blood(From enrollment to the last clinical follow-up at month 12)