A Master Protocol Empowering Mechanobiology Translation Research in Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Master Protocol Empowering Mechanobiology Translation Research in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Verification that the patient could not be reached for informed consent in accordance with applicable national regulations or, alternatively, TIER1 written Informed consent. Patients ≥18 years of age. Previous diagnosis of breast cancer, or a strong suspicion of BC based on clinical and radiological findings. ECOG Performance status < 2 (only for TIER1-2). Exclusion Criteria: 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) Patient unable to comply with the study protocol owing to psychological, social or geographical reasons. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or syphilis infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort of BC patients<br>Stage-mixed cohort of at least 500 breast cancer patients through their course of treatment, until death or a minimum of 5 years. | Other: Observational<br>* Retrospective cohorts and Prospective observation of standard clinical practice<br>|

What is the study measuring?
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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 |