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

Beijing Friendship Hospital60 enrolled

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Locally Advanced Rectal Cancer (LARC)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Complete Response (CR) rate

The proportion of patients confirmed to have achieved complete response after neoadjuvant therapy, as assessed by endoscopy, imaging (pelvic MRI/chest-abdominal CT), digital rectal examination, and pathological evaluation. The assessment time point corresponds to T2 (8-14 weeks after the end of neoadjuvant therapy). Complete response requires: normal mucosa on endoscopy with negative biopsy; no residual tumor on imaging; no palpable mass on digital rectal examination; and no viable tumor cells in postoperative pathology (if surgery is performed).

Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)

Secondary Outcomes

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)

The proportion of patients with ≤10% residual tumor cells and no lymph node metastasis in postoperative pathological examination, assessed at T3 (1 month after radical resection, corresponding to the technical roadmap).

Time frame: 1 month after surgery

Objective Response Rate (ORR)

The proportion of patients who achieve complete response (CR) or partial response (PR) after neoadjuvant therapy, assessed at T2 (8-14 weeks after the end of neoadjuvant therapy). Partial response is defined as a ≥30% reduction in tumor size confirmed by endoscopy and imaging, with no new lesions.

Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)

Disease-Free Survival (DFS)

The time from the initiation of neoadjuvant therapy to disease recurrence (confirmed by endoscopy/imaging), metastasis, or death from any cause, with follow-up through T4 (surveillance period of 3-6 months, optional) and subsequent long-term follow-up nodes as per the technical roadmap.

Time frame: Monitoring Period: Every 3 or 6 months after treatment completion, continued until 1 year.

Overall Survival (OS)

Time from randomization to death from any cause, recurrence, or metastasis. This serves as a gold-standard endpoint for assessing the long-term efficacy of anticancer therapy.

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)

The proportion of patients who avoid radical surgery and retain anal function and rectal organ integrity after neoadjuvant therapy, assessed at T3 (1 month after surgery for operated patients, or 1 month after treatment plan confirmation for non-operated patients, corresponding to the technical roadmap).

Time frame: 1 month after surgery

Neoadjuvant Therapy Score for Rectal Cancer (NAR)

At T2 (8-14 weeks after the end of neoadjuvant therapy), the patient's response to neoadjuvant therapy is evaluated using a standardized scoring system that integrates endoscopic findings, imaging regression, and tumor marker levels.

Time frame: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)

Quality of Life (QoL)

Assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Colorectal Cancer-Specific Module (EORTC QLQ-CR29) to evaluate physical function, psychological status, and bowel-related quality of life. The EORTC QLQ-C30 uses a 0-100 scale where higher scores in functional domains indicate better function, and higher scores in symptom domains indicate worse symptoms. The EORTC QLQ-CR29 uses a 0-100 scale where higher scores in symptom domains indicate worse bowel/rectal symptoms.

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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts