Application and Exploration of Personalized ctDNA-MRD Detection Technology in Predicting the Efficacy of Neoadjuvant Therapy for Rectal Cancer

Overview

This study is a single-center, prospective, observational clinical trial enrolling patients with locally advanced rectal cancer (cT3-4aN0M0 and cT1-4aN1-2M0). By collecting tissue and blood samples at multiple timepoints, and integrating multi-omics data including ctDNA mutations, copy number variations, and mtDNA profiles, a multi-omics model will be constructed to predict the efficacy of neoadjuvant therapy for rectal cancer.

Detailed description

This study is a single-center, prospective, observational clinical trial designed to construct and validate a multi-omics-based predictive model for neoadjuvant treatment efficacy in locally advanced rectal cancer. Patients diagnosed with locally advanced rectal cancer (cT3-4aN0M0 and cT1-4aN1-2M0) are enrolled, and tissue and blood samples are dynamically collected at multiple time points. By simultaneously analyzing plasma circulating tumor DNA (ctDNA) somatic mutations, copy number variations, and mitochondrial DNA (mtDNA), a multi-dimensional molecular biomarker system is constructed.The primary objectives of the study include: first, prospectively validating the efficacy of a multi-dimensional molecular biomarker model based on ctDNA mutations, mtDNA, and copy number variations for detecting molecular residual disease (MRD) during neoadjuvant therapy and assessing its sensitivity and specificity in predicting pathological response; second, comparing the sensitivity and specificity of different omics features-ctDNA mutations, mtDNA, copy number variations, alone or in combination-in predicting treatment efficacy after surgery.The secondary objectives are: first, to construct a multi-omics model integrating ctDNA mutations, copy number variations, and mtDNA for dynamically assessing tumor burden changes during neoadjuvant therapy; second, to explore and optimize ctDNA-MRD detection technology, aiming to overcome the high sample volume requirements of traditional methods and improve the detection rate of low-abundance ctDNA.

Interventions

• Diagnostic test Personalized ctDNA-MRD Detection
  This observational study involves collecting clinical data and biospecimens (peripheral blood and tissue samples) from participants at multiple timepoints. Personalized ctDNA-MRD detection technology, together with copy number variation and mtDNA profiling, is applied to analyze the samples. The primary goal is to predict neoadjuvant therapy efficacy by identifying biomarkers associated with key outcomes, such as tumor regression grade and pathological complete response rate. No experimental dru

Primary outcome measures

• Complete Response (CR) rate [Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)]

Secondary outcome measures (8)

• Complete Response Rate (CR) [Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)]
• Major Pathological Response Rate (MPR) [Time frame: 1 month after surgery]
• Objective Response Rate (ORR) [Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)]
• Disease-Free Survival (DFS) [Time frame: Monitoring Period: Every 3 or 6 months after treatment completion, continued until 1 year.]
• Overall Survival (OS) [Time frame: From the randomization date to the date of death from any cause, disease recurrence, or metastasis-whichever occurred first-assessed over the entire study period with a planned maximum follow-up of 12 months.]
• Organ Preservation Rate (OPR) [Time frame: 1 month after surgery]
• Neoadjuvant Therapy Score for Rectal Cancer (NAR) [Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)]
• Quality of Life (QoL) [Time frame: Baseline (T0), within 2 weeks after completion of radiotherapy (T1), 8-12 weeks after completion of radiotherapy (T2), and 4 weeks after surgery or after final treatment regimen determination (T3), through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• 1: Signed a written informed consent form and voluntarily participated in this study
• 2: Aged 18-75 years, regardless of sex
• 3: Histopathologically confirmed rectal adenocarcinoma
• 4: Clinical stage II-III as assessed by MRI (according to the AJCC 8th edition)
• 5: Distance from the lower tumor margin to the anal verge ≤10 cm
• 6: Surgically resectable
• 7: Able to swallow tablets normally
• 8: ECOG PS 0-1
• 9: No prior antitumor therapy for rectal cancer, including radiotherapy, chemotherapy, or surgery
• 10: Scheduled to undergo surgical treatment after completion of neoadjuvant therapy
• 11: No surgical contraindications
• 12: Normal function of major organs, including: complete blood count, blood biochemistry, and coagulation function

Exclusion criteria

• 1: History of allergy to monoclonal antibodies, any component of tislelizumab, or capecitabine
• 2: Prior or ongoing receipt of any tumor-directed surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc
• 3: Presence of any active autoimmune disease or history of autoimmune disease
• 4: History of immunodeficiency, including a positive HIV test result, other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation
• 5: Poorly controlled cardiac clinical symptoms or diseases, including but not limited to: heart failure of NYHA class II or above, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia that remains poorly controlled without or despite clinical intervention
• 6: Diagnosis of another malignancy within 5 years prior to the first use of the study drug, except for malignancies with low risk of metastasis or death (5-year survival rate >90%), such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, which may be considered for inclusion
• 7: Pregnant or lactating women
• 8: Other factors, as judged by the investigator, that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring concomitant treatment, alcohol abuse, drug abuse, family or social factors, or any condition that may affect the safety or compliance of the participant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Beijing Friendship Hospital — Beijing

Identifiers

NCT: NCT07393048 · MR-11-26-002019

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗