Plasma Multi - Omics Detection for Evaluating Efficacy and Recurrence Risk in Oligometastatic Colorectal Cancer Conversion Therapy

N/AActive Not RecruitingNCT07492238

Xiujuan Qu120 enrolled

Overview

This prospective study (PMEIRR-OCCCT) evaluates the utility of plasma multi-omics-including circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), proteomics, and metabolomics-in assessing response to conversion therapy and predicting recurrence in 120 patients with oligometastatic colorectal cancer (≤5 liver and/or lung metastases). Blood samples are collected at predefined timepoints: before conversion therapy, 3-6 weeks post-therapy, within 2 months after surgery or non-radical treatment, and during 24-month follow-up. Patients are stratified into radical vs. non-radical treatment groups based on post-conversion resectability. Tumor assessments (CT/MRI and CEA/CA19-9) occur every 3-4 months. The primary endpoint is progression-free survival (PFS) stratified by MRD status (ctDNA-negative vs. ctDNA-positive). Secondary endpoints include objective response rate (ORR), overall survival (OS), and duration of no evidence of disease (NED). The study aims to identify multi-omic biomarkers for early recurrence prediction and personalized intervention.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Enrollment

120

Conditions

Colorectal Cancer

Interventions

Description: This study utilizes a holistic plasma multi-omics approach, integrating circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), proteomics, and metabolomics to evaluate treatment response. Unlike conventional single-marker studies, this integration captures diverse biological signals-from genomic alterations to metabolic shifts-providing a superior assessment of efficacy and recurrence risk in oligometastatic CRC. All participants, regardless of their subsequent treatment path (radical or non-radical), undergo standardized blood collection at key clinical milestones: baseline, post-conversion therapy, and throughout a 2-year follow-up period. This allows for a continuous molecular "snapshot" of the disease, enabling the identification of MRD-positive patients who may require intensified intervention.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed oligometastatic colorectal cancer with ≤5 liver and/or lung metastases. * Assessed as potentially resectable by multidisciplinary team (MDT) and planned for neoadjuvant conversion therapy. * Age 18-75 years. * Estimated survival ≥6 months. * Willingness to provide blood samples and undergo long-term follow-up. * Signed informed consent. Exclusion Criteria: * Pregnant or breastfeeding individuals. * Uncontrolled medical conditions that could interfere with study assessments. * Significant cardiac, neurological, or other severe comorbidities. * History of other malignancies.

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) in MRD-Negative and MRD-Positive Groups

The primary outcome is progression-free survival (PFS), stratified by minimal residual disease (MRD) status. PFS is defined as the time from treatment initiation to the first occurrence of tumor recurrence, disease progression, or death from any cause, whichever occurs first. Tumor assessments are performed every 3-4 months for up to 24 months using imaging (CT or MRI) and serum tumor markers (CEA and CA19-9). Blood samples are collected at predefined time points to determine MRD status via ctDNA analysis, which informs individualized treatment decisions. Differences in PFS between MRD-negative and MRD-positive groups are evaluated using the Kaplan-Meier method and log-rank test, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated using Cox proportional hazards regression.

Time frame: From treatment initiation through 24 months, with assessments at each follow-up visit every 3-4 months.

Secondary Outcomes

Objective Response Rate (ORR)

Proportion of patients with tumor volume reduction ≥30% and maintained for ≥4 weeks, including complete response (CR) and partial response (PR).

Time frame: Assessed at the first tumor evaluation visit, 8 weeks after treatment initiation.

Overall Survival (OS)

Time from treatment initiation to death from any cause.

Time frame: Monitored continuously from treatment initiation through 24 months, with survival status updated every 3-4 months.

Disease-Free State (NED)

Absence of detectable tumor via imaging and clinical examination after treatment.

Time frame: Evaluated at each follow-up visit during the 24-month period.

ctDNA and cfRNA Dynamic Changes

Longitudinal changes in ctDNA and cfRNA levels in blood samples collected at multiple time points.

Time frame: Measured via NGS sequencing at predefined time points: before conversion therapy, 3-6 weeks after conversion therapy, within 2 months after surgery or non-radical treatment, and during follow-up.