A Master Protocol Empowering Mechanobiology Translation Research in Breast Cancer (METAMECH)

METAMECH is a master observational protocol designed to empower a bi-directional collaboration between basic and clinical research, an essential prerequisite to feed and implement precision oncology.

METAMECH will follow a stage-mixed cohort of at least 500 patients through their course of treatments, until death or a minimum of 5 years. Patients will be longitudinally sampled and matched clinical data (including imaging) will be collected. Via a multi-tiered informed consensus process, METAMECH will also allow to develop companion diagnostics for molecular enrichment strategies in AIRC-driven proof-of-concept trials.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Observational

Detailed Description

METAMECH has been designed to streamline the study of the co-evolutionary landscape between tumor and host cells in a cohort of breast cancer (BC) patients, with the aim of understanding how their outcomes can be significantly improved (e.g. reduction of their chance of recurrence and survival improve). This clinical resource for integrative clinical data and sample collection will allow to generate hypotheses on mechanisms supporting the outgrowth of human metastases, mine for new potentially actionable targets and the selection of appropriate patients for experimentally-driven trials. To achieve the required level of 'experimental precision', patients will enter METAMECH at two different 'therapeutic checkpoints': i) prior to a tumor sampling event (surgery, biopsy) or ii) prior to any line of treatment.

To optimize the enrollment of patients, the longitudinal collection of data/samples and their logistic management, METAMECH has been designed as a flexible infrastructure organized in Tiers for the stepwise comprehension of the biological processes that drive tumor evolution, and precisely:

• TIER0, Retrieving: the ability to retrospectively retrieve clinically annotated BC archival samples to validate/discover new mechanotransduction-linked biomarkers;
• TIER1, Recording: the ability to prospectively record BC characteristics under standard of care treatments and to define new mechanotransduction-linked biomarkers;
• TIER2, Modelling: the ability to develop pertinent experimental models to study the aberrant mechanisms underlying the metastatic outgrowth and define mechanotransduction-targeting therapeutic strategies;
• TIER3, Linking: the ability to access data and samples of patients enrolled in POC trials to prove the efficacy and study/understand resistance mechanisms of mechanotransduction-targeting therapies.

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Smeralda Rapisarda; Phone Number: +3902574303236; Email: clinical.trials@ifom.eu
• Study Contact Backup: Name: Ylenia Silvestri, PhD; Phone Number: +3902574303799; Email: clinical.trials@ifom.eu

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • Not yet recruiting
    • Asst Papa Giovanni XXIII
    • Principal Investigator: Vittoria Fotia, MD
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS, Istituto Nazionale dei Tumori
    • Principal Investigator: Filippo De Braud, MD
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS, Istituto Neurologico Carlo Besta
    • Principal Investigator: Cecilia Casali, MD
  • Milano, Italy, 20089
    • Recruiting
    • IRCCS Humanitas
    • Principal Investigator: Alberto Zambelli, MD
  • Milano, Italy, 20141
    • Recruiting
    • IEO - Istituto Europeo di Oncologia
    • Principal Investigator: Viviana Galimberti
  • Novara, Italy, 28100
    • Recruiting
    • Azienda Ospedaliero Universitaria Maggiore della Carita di Novara
    • Principal Investigator: Alessandra Gennari, MD
  • Padova, Italy, 35128
    • Recruiting
    • Istituto Oncologico Veneto IRCCS (IOV)
    • Principal Investigator: Valentina Guarneri, MD
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS, Policlinico San Matteo Pavia
    • Principal Investigator: Paolo Pedrazzoli, MD
  • Reggio Emilia, Italy, 42122
    • Recruiting
    • Azienda U.S.L. - IRCCS di Reggio Emilia
    • Principal Investigator: Filippo Giovanardi, MD
  • Roma, Italy, 00144
    • Recruiting
    • Istituto Nazionale Tumori Regina Elena di Roma - Istituti Fisioterapici Ospitalieri (IFO)
    • Principal Investigator: Giovanni Blandino, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage-mixed Breast Cancer (BC) patients

Description

Inclusion Criteria:

1. Verification that the patient could not be reached for informed consent in accordance with applicable national regulations or, alternatively, TIER1 written Informed consent.
2. Patients ≥18 years of age.
3. Previous diagnosis of breast cancer, or a strong suspicion of BC based on clinical and radiological findings.
4. ECOG Performance status < 2 (only for TIER1-2).

Exclusion Criteria:

1. Any other current malignancy or malignancy diagnosed or relapsed within the past 5 years (other than non-melanomatous skin cancer, stage 0 melanoma in situ, and in situ cervical cancer)
2. Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
3. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or syphilis infection.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort of BC patients; Stage-mixed cohort of at least 1500 breast cancer patients through their course of treatment, until death or a minimum of 5 years.	Other: Observational; Retrospective cohorts and Prospective observation of standard clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients recruited in TIER0 and TIER 1	Number of recruited BC cases in TIER 0 and in TIER 1 with complete clinically annotated FFPE and/or frozen biological samples	6 months
Number of patients recruited in TIER2	Number of recruited BC cases in TIER 2	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients triaged in proof-of concept (POC) clinical trials	Number of BC cases recruited in TIER 3	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New prognostic mechanotransduction-linked markers	Number of identified/validated new prognostic mechanotransduction-linked markers	6 months
New predictive mechanotransduction-linked markers	Number of identified/validated new predictive mechanotransduction-linked markers	6 months
Biomarkers correlation with RR	Correlation between identified biomarkers with therapies response rates (RR)	6 months
Biomarkers correlation with PFS	Correlation between identified biomarkers with progression-free survival (PFS)	6 months
Biomarkers correlation with OS	Correlation between identified biomarkers with overall survival (OS)	6 months

Collaborators and Investigators

• Sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology
• Investigators: Study Chair: Silvia Marsoni, MD, IFOM ETS - The AIRC Institute of Molecular Oncology

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IFOM-CPO007/2019/PO006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No