A Study of Biological, Genetic, and Constitutional Factors and Non-invasive Monitoring to Assess Personal Cancer Risks

NCT07469709 | Recruiting

• 1 other identifier: 032-FPO22
• Study Type: observational
• Target: 850
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer; Colo-rectal Cancer; Ovarian Cancer; Melanoma (Skin Cancer); Non-Small Cell Lung Cancer (MeSH Term: Carcinoma, Non-Small-Cell Lung)

Outcome Measures

Primary Outcomes (1)

• Number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours

  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

  From enrollment to the last clinical follow-up at month 12

Secondary Outcomes (2)

• 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

Other Outcomes (1)

• Qualitative outcomes: Characterisation of the level of differentiation and clonal heterogeneity of the T lymphocyte repertoire in the context of different tumours

  At enrollment

Study Arms (5)

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).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

600 patients known to have breast cancer (N=200), ovarian cancer (N=200) and colon cancer (N=200) will be evaluated. Based on the results of the germline genetic test, patients will be classified into three cohorts: * COHORT 2A, individuals who are carriers of hereditary traits (probands) * COHORT 2B, subjects identified by genetic counselling as being at risk of being carriers of hereditary neoplastic syndrome, not confirmed by genetic testing * COHORT 2C, an additional subgroup of patients (N=150), 50 for each type of tumour, who tested negative in diagnostic genetic analysis. COHORT 3 includes 250 patients who underwent radical surgery: * locally advanced breast cancer with triple-negative phenotype or lobular histology * high-grade serous ovarian cancer * metastatic melanoma * stage IIB and IIIA non-small cell lung cancer * colon cancer with lymph node involvement and vascular invasion

You may qualify if:

• 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.

You may not qualify if:

• Age \<18 years;
• Unwillingness or inability to give informed consent

Sponsors & Collaborators

• Fondazione del Piemonte per l'Oncologia: lead

Study Sites (1)

Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo

Candiolo, Turin, 10060, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

tumor tissue and blood

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Ovarian Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chiara Lazzari, MD

  Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo

  STUDY CHAIR

• Federico Bussolino, MD

  Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo

  STUDY CHAIR

• Luigia Pace, PhD

  Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo

  STUDY CHAIR

Central Study Contacts

Vanesa Gregorc, MD

CONTACT

+390119933915; vanesa.gregorc@ircc.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2026
• First Posted: March 13, 2026
• Study Start: February 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)