Breast Cancer, Cervical Cancer, Colorectal Cancer, Gastric Cancer, Head and Neck Cancer (H&N)
Conditions
Keywords
Microbiome, Cancer, Immunotherapy, Tumor microenvironment, Biomarkers, Metagenomics, Transcriptomics, Metabolomics
Brief summary
This is a prospective observational cohort study conducted at Fundación CTIC in Bogotá, Colombia. It characterizes the oral, fecal and intratumoral microbiome of Colombian adults with advanced solid tumors (gastric, colorectal, breast, cervical and head-and-neck cancer) who receive first-line immunotherapy as standard of care, and compares them with healthy volunteers. Using multi-omics (HiFi metagenomics, 16S, tumor RNA-Seq and untargeted metabolomics), the study aims to identify microbial signatures associated with treatment response and survival, building the initial Colombian cohort of a Cancer Microbiome Atlas with Latin American projection.
Detailed description
Single-center, prospective, observational cohort study. 120 patients with advanced (stage III unresectable or IV) solid tumors candidates for first-line immunotherapy and 30 healthy controls are enrolled (total N=150). Patients provide saliva, stool and tongue-scraping samples plus archival FFPE tumor tissue at baseline (V0) and at 6 (V1) and 12 (V2) months; controls provide saliva and stool at V0 only. Microbiomes are profiled by PacBio HiFi shotgun metagenomics and full-length 16S; tumor transcriptome by RNA-Seq; and saliva/stool metabolome by GC-MS in a subcohort (n=60). Tumor response is assessed by RECIST 1.1. Microbial, transcriptomic and metabolomic features are integrated with clinical outcomes (objective response, PFS, OS) using multivariable and machine-learning models.
Interventions
DRUGFirst-line immunotherapy (immune checkpoint inhibitors), INVIMA-approved, standard of care
Exposure observed: first-line immunotherapy with immune checkpoint inhibitors administered as standard of care (INVIMA-approved); no experimental intervention is assigned by the study. Healthy controls receive no immunotherapy.
Sponsors
Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo
American Society of Clinical Oncology
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age 18 years or older. * Histologically confirmed advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer. * Candidate for first-line immunotherapy per current clinical guidelines. * Available FFPE tumor block in institutional or reference pathology archive. * Able to provide saliva and stool samples at V0 and follow-up. * ECOG performance status within protocol limits; life expectancy over 3 months. * Cognitive capacity to give informed consent; signed EVA-BIOBANCO and Atlas consents. Inclusion Criteria (healthy controls) * No prior cancer diagnosis. * No active autoimmune disease; no inflammatory bowel disease. * No antibiotics, invasive dental treatment, immunosuppressants or corticosteroids in the prior 3 months; no severe active periodontal disease.
Exclusion criteria
* Systemic antibiotics within 3 months (except short course under 5 days for uncomplicated infection). * Probiotics or prebiotics within 30 days. * Chronic proton-pump inhibitors for more than 3 continuous months. * Inflammatory bowel disease (Crohn, ulcerative colitis) or extensive bowel resection. * Pregnancy or lactation. * BMI under 18.5 or over 40 kg/m². * Uncontrolled diabetes (HbA1c at or above 9% in prior 3 months). * Invasive dental treatment within 3 months. * Patients: simultaneous randomized trial of a non-INVIMA-approved experimental immunotherapy; or no evaluable FFPE block meeting quality thresholds. * Inability to ensure 12-month clinical follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral, fecal and intratumoral microbiome signatures associated with objective tumor response (RECIST 1.1) to first-line immunotherapy | Baseline (V0) and through 12 months | Characterization of oral, fecal and intratumoral microbiomes and identification of taxa and diversity metrics differentiating responders (CR+PR) from non-responders (SD+PD) by RECIST 1.1. |
| Differences in microbiome composition and diversity between cancer patients and healthy controls | Baseline (V0) | Comparison of alpha and beta diversity and differential taxonomic and functional abundance between cancer patients and healthy controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbial, transcriptomic and metabolomic biomarkers associated with progression-free survival (PFS) | Association of microbial diversity, key taxa, MAGs and functional pathways with progression-free survival, estimated by Kaplan-Meier and adjusted Cox models. | Up to 36 months |
| Microbial biomarkers associated with overall survival (OS) | Up to 36 months | Association of microbiome features with overall survival, estimated by Kaplan-Meier and adjusted Cox models. |
Countries
Colombia
Contacts
CONTACTAndrés F Cardona, MD, MSc, PhD, MBA
CONTACTLiliana Gutiérrez, RN, MSc
PRINCIPAL_INVESTIGATORAndrés F Cardona, MD, MSc, PhD, MBA
Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
Outcome results
None listed