Colon Cancer, Colorectal Cancer, Rectal Cancers
Conditions
Keywords
microRNA, microbiome, stool biomarkers, saliva biomarkers, colorectal cancer, anastomotic leak, diet, recurrence
Brief summary
This multicenter prospective interventional study will evaluate stool and saliva microRNA expression and microbiome composition in patients with histologically confirmed colon or rectal cancer during key phases of the diagnostic and therapeutic pathway. The study aims to confirm and refine molecular signatures associated with colorectal cancer, assess the diagnostic and prognostic potential of salivary biomarkers, and characterize dynamic molecular changes during treatment and follow-up
Detailed description
MIMICC is a multicenter prospective interventional academic study sponsored by Fondazione del Piemonte per l'Oncologia - IRCCS Istituto di Candiolo. Approximately 2,500 patients with histologically proven colon or rectal cancer will be enrolled. Biological samples will include stool and saliva collected at protocol-defined time points during the diagnostic and therapeutic pathway; at the sponsor center, FFPE tissue and blood/plasma samples may also be collected for additional molecular analyses. The study will investigate microbiome composition and miRNA expression profiles at diagnosis, after neoadjuvant treatment when applicable, at surgery, during postoperative follow-up, during systemic treatment, and at recurrence. Clinical, dietary, and lifestyle data will be integrated with molecular data to identify and refine biomarkers for diagnosis, prognosis, treatment response, surgical complications, and recurrence risk. Initial sample collection will be performed for approximately 4 months at the sponsor center before extension to the collaborating centers.
Interventions
OTHERProspective Biological Sample Collection and Longitudinal Molecular Profiling
Protocol-defined collection of stool and saliva samples at diagnosis/baseline, after neoadjuvant treatment when applicable, at surgery after bowel preparation, at the time of anastomotic leak when applicable, 30 days after surgery, at day 0 of chemotherapy when applicable, at the end of chemotherapy, and at recurrence. At the sponsor center, FFPE tissue and blood/plasma samples may also be collected. Molecular analyses include microbiome profiling, miRNA sequencing, and mutational profiling on FFPE tissue
OTHERDiet and Lifestyle Assessment
Administration of the EPIC food frequency questionnaire and the WCRF diet/lifestyle score at diagnosis and approximately 1 year later, with integration of BMI and physical activity data.
Sponsors
Fondazione del Piemonte per l'Oncologia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
All enrolled participants will undergo prospective longitudinal collection of biological samples and study-specific clinical, dietary, and lifestyle data at protocol-defined time points during their standard diagnostic and therapeutic pathway for colorectal cancer. The study will start with an initial sponsor-center phase and will subsequently expand to the collaborating centers
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed colon or rectal cancer on endoscopic biopsy * Any T stage, any N stage, M0-M1, candidate for surgical intervention * Colon tumors with indication for surgical resection with curative intent, including right hemicolectomy, left hemicolectomy, transverse colon resection, colectomy, or total proctocolectomy * Rectal tumors with indication for upfront surgery or neoadjuvant chemoradiotherapy * Written informed consent signed before any study procedure * Age between 18 and 75 years
Exclusion criteria
* Tis/T1 lesions or lesions almost completely resected by endoscopic polypectomy/EMR/ESD * Use of immunosuppressive or immunomodulatory drugs within the previous 6 months * Current or previous diagnosis of other solid or hematologic malignancies * Inability or refusal to provide informed consent * Inability or refusal to be followed at the study institution/network
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic accuracy of fecal microbiome and fecal microRNA molecular signatures | At diagnosis/baseline, before surgery or at least 30 days after bowel preparation for colonoscopy | Diagnostic performance of predefined and refined fecal microbiome and fecal microRNA signatures, assessed using measures such as sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve for clinically relevant colorectal cancer classifications |
| Diagnostic and prognostic performance of salivary microbiome and microRNA molecular signatures | From baseline sample collection through follow-up, up to 2 years | Diagnostic and prognostic performance of salivary microbiome and microRNA profiles, assessed by classification metrics and association with disease course, treatment response, and recurrence |
| Longitudinal change in stool and saliva microbiome and microRNA profiles | From diagnosis/baseline through recurrence or up to 2 years after enrollment | Within-participant changes in stool and saliva microbiome composition and microRNA expression profiles across the protocol-defined diagnostic and therapeutic time points. |
| Integrated colorectal cancer microbiome/microRNA atlas dataset | From enrollment through study completion, up to 4 years | Number of participants with analyzable integrated molecular and clinical datasets contributing to the colorectal cancer-specific microbiome/microRNA atlas. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Molecular signatures in patients receiving neoadjuvant treatment | From baseline to end of neoadjuvant treatment, up to 6 months | Definition and characterization of stool microbiome and microRNA signatures in participants treated with neoadjuvant total neoadjuvant therapy or chemoradiotherapy |
| Biomarker profiles in participants with microsatellite instability-high tumors | From baseline through end of standard treatment and follow-up, up to 2 years | Identification of microbiome and microRNA biomarkers associated with treatment response in participants with MSI-High colorectal cancer |
| Effect of bowel preparation on fecal microbiome and microRNA profiles | From preoperative/pre-intervention baseline to intraoperative sample collection | Changes in fecal microbiome and microRNA markers after different bowel preparation strategies, with or without associated antibiotic therapy |
| Biomarker profiles associated with early-onset colorectal cancer | At diagnosis/baseline | Identification of stool microbiome and microRNA signatures associated with early-onset colorectal cancer. |
| Microbiome and microRNA profiles associated with anastomotic leak | From surgery to first documented anastomotic leak, assessed during postoperative follow-up up to 30 days after surgery | Association between molecular profiles and the occurrence of anastomotic leak after colorectal surgery |
| Association of diet, body mass index, and physical activity with microbiome and microRNA profiles | From diagnosis to approximately 1 year after diagnosis | Association between diet/lifestyle variables and stool/saliva microbiome and microRNA profiles. |
| Tumor mutational profile in FFPE tissue | From tissue collection during routine diagnostic or surgical procedures through study completion, up to 4 years | Mutational profiling of FFPE colorectal cancer tissue to integrate genomic data with microbiome and microRNA findings |
Countries
Italy
Contacts
CONTACTFelice Borghi, MD
Outcome results
None listed