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

March 9, 2026 updated by: Fondazione del Piemonte per l'Oncologia

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

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

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

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. Patients will be selected before surgery and, if they agree to participate in the study, they will sign the informed consent in an oncogenetics consultancy context.

The selected patients will undergo blood sampling (5 ml in EDTA tubes) for the extraction of nucleic acids (DNA and RNA).

Based on the result of germline genetic testing, patients will be classified into 3 cohorts:

  • 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, a further subgroup of patients (N=150), 50 for each type of tumor, negative results in diagnostic genetic analysis. In selected patients in cohort 2C, DNA/RNA will be analyzed for the identification of causative genetic variants in genes that have escaped routine diagnostic investigation.

Moreover, a further cohort of patients will be selected, COHORT 3 which includes 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).

Patients enrolled in COHORTS 2A, 2B and 3 will undergo the following blood draws for WP2:

  • 20 ml in Cell-Free DNA BCT® CE tubes (Streck) for ctDNA analysis. Samples are centrifuged at 1600 (±150) g for 10 minutes at room temperature. After centrifugation, the plasma is subjected to further centrifugation for 10 minutes at 3000 (±150) g.
  • 20 ml in Cell Save tubes for the isolation of CTCs.
  • 30 ml for the study of circulating immune populations (WP3). Furthermore, the tumor tissue taken during the surgical phase will be collected and analyzed in WP4 and for the study of the microenvironment with "Next Generation Sequencing" techniques applied to the tumor as a whole and at the single cell level and to the immune populations (TILs).

Study Type

Observational

Enrollment (Estimated)

850

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Turin
      • Candiolo, Turin, Italy, 10060
        • Recruiting
        • Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
Time Frame: 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
From enrollment to the last clinical follow-up at month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of isolated circulating tumour cells (CTCs) in patients' blood
Time Frame: From enrollment to the last clinical follow-up at month 12
The aim of this outcome is the correlation between the number of isolated circulating tumour cells (CTCs) and the clinical outcome
From enrollment to the last clinical follow-up at month 12
Amount of circulating tumour DNA (ctDNA) in patients' blood
Time Frame: From enrollment to the last clinical follow-up at month 12
The aim of this outcome is the correlation between the detection of circulating tumour DNA (ctDNA) and the clinical outcome
From enrollment to the last clinical follow-up at month 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Qualitative outcomes: Characterisation of the level of differentiation and clonal heterogeneity of the T lymphocyte repertoire in the context of different tumours
Time Frame: At enrollment

Patients who will undergo standard preoperative drug treatment will also have blood samples taken before the start of treatment and before surgery. The collected material will undergo the following analyses:

  • Phenotypic study using multiparametric cytometry of lymphocyte subpopulations.
  • Transcriptional profiling using sc-RNA sequencing (scRNA-seq) and surface markers
  • Longitudinal flow cytometric analysis of the specific response of tumour-infiltrating and peripheral T lymphocytes against tumour neoepitopes.
  • Single-cell multiomics analysis of the T lymphocyte response to specific neoepitopes identified in the tumour.
  • Study of chromatin structure in different subpopulations of TILs in patients with or without neoplastic progression.
  • Evaluation of the functional activation profile, memory properties, epigenetic profile, and inter- and intra-clonal heterogeneity
At enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione del Piemonte per l'Oncologia

Investigators

  • Study Chair: 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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2024

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 3, 2026

First Submitted That Met QC Criteria

March 9, 2026

First Posted (Actual)

March 13, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 032-FPO22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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