Investigation of the Value of ctDNA in Diagnosis, Treatment, and Surveillance of Surgically Resectable Colorectal Cancer

Study Overview
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Brief Summary
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In this study, we aim to investigate the value of circulating tumor DNA (ctDNA) analysis in the diagnosis, treatment, and surveillance of patients with surgically resectable colorectal cancer, by performing serial analysis of ctDNA, next-generation sequencing of surgical specimens, and observation of patients undergoing radical resection of the tumor with or without adjuvant chemo- and/or radiotherapy.

Detailed Description
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A prospective, observational study to determine the value of circulating tumor DNA (ctDNA) for predicting the therapeutic effects of the combined modality treatment for colorectal cancer and the patients' long-term prognosis. Research objects: patients with surgically resectable colorectal cancer. After giving fully informed consent, the prospective participants will undergo the classical combined modality treatment according to NCCN guidelines. Serial analysis of ctDNA will be performed at specific time points including pre-treatment, (post-NCRT for NCRT patients), postoperative week 1, post-ACT, postoperative year 1, 2, and 3. The next-generation sequencing of surgical specimens will be performed as well. Participants will be observed and examined during the entire course of treatment and the follow-up period. The 3 year disease free survival (3y-DFS) will be the primary end-point.

Official Title
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Investigation of the Value of ctDNA Analysis in the Diagnosis, Treatment, and Surveillance of Patients With Surgically Resectable Colorectal Cancer

Conditions
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Rectal Cancer, Adenocarcinoma, Neoadjuvant Chemoradiation

Intervention / Treatment
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* Drug: Capecitabine +/- Oxaliplatin
* Procedure: local resection
* Procedure: radical resection
* Other: No adjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 75 years old. Patients with surgically resectable colorectal cancer, while without distal metastasis of the disease. Patients with ASA physical status scroe of I to III. Patients who can fully understand the content of the informed consent form and sign it upon their own opinions. Patients who can coordinate with the researchers to undergo the long-term post-treatment rechecks and follow-ups. Exclusion Criteria: Patient has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the evaluation of the patient (e.g., end-stage liver disease, pulmonary hypertension, systemic lupus erythematosis etc.). Patient is pregnant or lactating. Patient has a history of malignancy within 5 years except curatively treated basal cell carcinoma, squamous cell carcinoma in a non-mucosal, ultraviolet exposed area, or cervical carcinoma. Patient is participating in any other clinical trials within 30 days prior to screening. Patient has severe mental illness. Patient has any other conditions, which, in the opinion of the Investigator, would interfere with the evaluation of the subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT group<br>Group of patients with pathologically confirmed Stage II-III colorectal cancer who receive postoperative treatment with chemotherapeutic agent (ACT) using Capecitabine +/- Oxaliplatin. | Drug: Capecitabine +/- Oxaliplatin<br>* Patients in ACT group will undergo postoperative adjuvant chemotherapy with single agent Capecitabine regimen or combined Capecitabine +Oxaliplatin regimen.<br>|
| Experimental: Non-ACT group<br>Group of patients with pathologically confirmed stage II colorectal cancer who receive no adjuvant chemotherapy. | Other: No adjuvant chemotherapy<br>* Patients in Non-ACT group will not undergo postoperative adjuvant chemotherapy.<br>|
| Experimental: LR group<br>Group of patients with clinically staged T1-2N0 rectal cancer who undergo local resection (LR) | Procedure: local resection<br>* Patients in the LR group will undergo local resection of the T1-2N0 rectal carcinoma<br>* Other names: LR;|
| Experimental: RR group<br>Group of patients with clinically staged T1-2N0 rectal cancer who undergo radical resection (RR) | Procedure: radical resection<br>* Patients in the RR group will undergo radical resection of the T1-2N0 rectal carcinoma<br>* Other names: RR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5y DFS | The 5-year disease free survival rate of the patients. | 5 years | 
| 5y LR | The 5-year local recurrence rate of the patients. | 5 years | 
| 5y OS | The 5-year overall survival rate of the patients. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of ctDNA level after surgery | Changes of patients' ctDNA level after undergoing surgical resection of the tumor. | 1 month | 
| Changes of ctDNA level after adjuvant therapy | Changes of patients' ctDNA level after receiving adjuvant therapy (eg. adjuvant chemothearpy). | 6 months | 
| Changes of ctDNA level when disease recurs | Changes of patients' ctDNA level after disease recurrence happens | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, neoajuvant chemoradiation, circulating tumor DNA