Clinical trial NCT04120935: ALFAOMEGA Master Observational Trial
Official title: A Master Protocol Empowering Precision Research in Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer
Lead sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology
Sponsor class: OTHER
First posted: 2019-10-09
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Colorectal cancer patients

Brief summary: AlfaOmega has been designed to streamline the study of the co-evolutionary landscape between tumor and host cells in a cohort of CRC patients, with the aim of understanding how their outcomes can be significantly improved (e.g. reduction of their chance of recurrence and survival improval). This clinical resource for integrative clinical data and sample collection will allow the molecular story-telling of CRC metastatic spread along time and space and the selection of appropriate patients for experimentally-driven trials.

Detailed description: AlfaOmega is an observational study that 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, AlphaOmega will also allow to develop companion diagnostics for molecular enrichment strategies in AIRC-driven proof-of-concept trials. To achieve the required level of 'experimental precision', patients will enter AlphaOmega at two different 'therapeutic checkpoints': i) prior to a surgical event or ii) prior to a systemic treatment. In the latter case patients with no previous lines of therapy for metastatic disease will be privileged.

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

* TIER1, Monitoring: the ability to follow CRC evolution under standard of care treatments and to define new evolution-linked biomarkers. This will be achieved through the collection of clinical data, imaging data, FFPE tissue and frozen plasma/PBMC.
* TIER2, Modelling: the ability to develop pertinent experimental models to study evolutionary mechanisms and define evolution-targeting therapeutic strategies. This will be achieved through the collection of Fresh Tissue, Whole Blood, Stools, Buccal Swabs and other fluids.
* TIER3, Linking: the ability to access data and samples of patients enrolled in proof-of-concept trials to prove the efficacy and study/understand resistance mechanisms of evolution-targeting therapies. This will be achieved by introducing the connection in the trial protocol.

Eligibility criteria: Inclusion Criteria:

1. TIER1 written Informed consent.
2. Patients ≥18 years of age.
3. Previous diagnosis of colorectal cancer, or a strong suspicion of CRC based on clinical and radiological findings.
4. In patients with previous diagnosis of CRC availability of diagnostic Formalin-Fixed, Paraffin Embedded (FFPE) blocks (surgical resection and/or tumor biopsies), or at least 10 slides (preferably 20). FFPE tissue blocks are always preferred to slides.
5. ECOG Performance status \< 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 longitudinally monitored
timeFrame: 6 months
Secondary outcomes:
measure: Number of patients triaged in proof-of-concept (POC) clinical trials
timeFrame: 6 months
Other outcomes:
measure: Number of new prognostic and predictive biomarkers
timeFrame: 6 months
measure: Correlation of new prognostic and predictive biomarkers with clinical outcomes
timeFrame: 6 months
Locations:
city: Milan
country: Italy
facility: IRCCS Istituto Clinico Humanitas
state: MI
city: Milan
country: Italy
facility: Fondazione IRCCS, Istituto Nazionale dei Tumori
state: MI
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
state: Mi
city: Milan
country: Italy
facility: Niguarda Cancer Center - ASST Grande Ospedale Metropolitano Niguarda
state: MI
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IOV)
state: PD
city: Candiolo
country: Italy
facility: Istituto di Candiolo - IRCCS
state: Torino
city: Orbassano
country: Italy
facility: Azienda Ospedaliero Universitaria San Luigi Gonzaga
state: Torino
city: Biella
country: Italy
facility: ASL di Biella - Ospedale degli Infermi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Luigi Vanvitelli
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Ravenna
country: Italy
facility: AUSL della Romagna - Ospedale Santa Maria delle Croci
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano
city: Barcelona
country: Spain
facility: Hospital del Mar - Parc de Salut Mar
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Barcelona
country: Spain
facility: Hospital de Sant Joan Despí Moises Broggi
city: Barcelona
country: Spain
facility: Hospital Moises Broggi
city: Valencia
country: Spain
facility: INCLIVA - Instituto de Investigatión Sanitaria
Study officials:
affiliation: IFOM ETS - The AIRC Institute of Molecular Oncology
name: Silvia Marsoni, MD
role: PRINCIPAL_INVESTIGATOR
References: