Atlas of the Oral, Fecal and Intratumoral Microbiome of Colombian Patients With Advanced Solid Tumors Candidates for First-Line Immunotherapy - Initial Phase of a Project With Latin American Projection
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Oral, fecal and intratumoral microbiome signatures associated with objective tumor response (RECIST 1.1) to first-line immunotherapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Patients with advanced solid tumors
120 Colombian adults with advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer, candidates for first-line immunotherapy (standard of care). Saliva, stool and tongue scraping collected at V0, V1 (6 mo) and V2 (12 mo); archival FFPE tumor block retrieved at V0.
干预措施: First-line immunotherapy (immune checkpoint inhibitors), INVIMA-approved, standard of care (Drug)
Healthy controls
30 healthy adult volunteers without prior cancer, active autoimmune disease or inflammatory bowel disease, and without antibiotics or invasive dental treatment in the prior 3 months. Saliva and stool collected at V0 only; no longitudinal follow-up.
结局指标
主要结局
Oral, fecal and intratumoral microbiome signatures associated with objective tumor response (RECIST 1.1) to first-line immunotherapy
时间窗: 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
时间窗: Baseline (V0)
Comparison of alpha and beta diversity and differential taxonomic and functional abundance between cancer patients and healthy controls.
次要结局
- 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.)
- Microbial biomarkers associated with overall survival (OS)(Up to 36 months)