Clinical trial NCT04625023: A Master Protocol Empowering Mechanobiology Translation Research in Breast Cancer
Official title: A Master Protocol Empowering Mechanobiology Translation Research in Breast Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Lead sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage-mixed Breast Cancer (BC) patients

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients recruited in TIER0 and TIER 1
timeFrame: 6 months
measure: Number of patients recruited in TIER2
timeFrame: 6 months
Secondary outcomes:
measure: Number of patients triaged in proof-of concept (POC) clinical trials
timeFrame: 6 months
Other outcomes:
measure: New prognostic mechanotransduction-linked markers
timeFrame: 6 months
measure: New predictive mechanotransduction-linked markers
timeFrame: 6 months
measure: Biomarkers correlation with RR
timeFrame: 6 months
measure: Biomarkers correlation with PFS
timeFrame: 6 months
measure: Biomarkers correlation with OS
timeFrame: 6 months
Locations:
city: Bergamo
country: Italy
facility: Asst Papa Giovanni Xxiii
city: Milano
country: Italy
facility: IRCCS Humanitas
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Fondazione IRCCS, Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Fondazione IRCCS, Istituto Neurologico Carlo Besta
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carità di Novara
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS (IOV)
city: Pavia
country: Italy
facility: Fondazione IRCCS, Policlinico San Matteo Pavia
city: Reggio Emilia
country: Italy
facility: Azienda U.S.L. - IRCCS di Reggio Emilia
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena di Roma - Istituti Fisioterapici Ospitalieri (IFO)
Study officials:
affiliation: IFOM ETS - The AIRC Institute of Molecular Oncology
name: Silvia Marsoni, MD
role: STUDY_CHAIR
References: