Evaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study

Not Applicable

Recruiting

• Conditions: Circulating Tumor DNA; Stage III Colorectal Cancer
• Interventions: Diagnostic Test: ctDNA dynamic monitoring

• Registration Number: NCT05161585
• Lead Sponsor: Fudan University

Brief Summary

For patients with stage III colon cancers, radical resection of primary tumor followed by adjuvant chemotherapy is currently the standard treatment. Adjuvant chemotherapy with 5-fluorouracil and oxaliplatin based regimen has been proved effective to improve recurrence-free survival and overall survival. Approximately half of patients with stage III colon cancers can be cured by surgery alone, while a substantial number of patients still experience recurrence, even with standard adjuvant chemotherapy. In recent years, circulating tumor DNA (ctDNA) has been detected in the cell-free component of peripheral blood samples in advanced colorectal cancers and many other solid tumors. Several previous studies have suggested that in patients with stage I-III colorectal cancer, postoperative ctDNA was an valuable biomarker to predict minimal residual disease (MRD) after radical resection, thus redefining patients risk outcome groups and guiding postoperative treatment. In addition, recent studies based on serial postoperative ctDNA detection showed that serial ctDNA analyses revealed disease recurrence up to 5-16.5 months ahead of radiological imaging. Here, based on the role of ctDNA in predicting MRD, we conducted an open, prospective, randomized controlled phase II cohort study to explore if ctDNA can as a biomarker to guide personalized surveillance strategy after surgery.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-01
• Study First Submitted: 2021-11-21
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-03
• Last Update Submitted: 2021-12-03
• Study First Posted: 2021-12-17
• Last Update Posted: 2021-12-17
• Primary Completion: 2022-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 316

Inclusion Criteria

• Age ≥ 18 and ≤80 years old, regardless of gender;
• Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0 ~ 2;
• Pathologically confirmed as stage III colorectal cancer;
• Radical operation performed ;
• With expected survival of more than 12 months;
• The subjects (or their legal representative / Guardian) must sign the informed consent form, indicating that they understand the purpose of the study, understand the necessary procedures of the study, and are willing to participate in the study.

Read More

Exclusion Criteria

• Neoadjuvant therapy performed before operation;
• Blood transfusion performed during operation or within 2 weeks before operation;
• Incomplete baseline samples, including preoperative plasma samples, surgical tumor tissue samples and plasma samples 3-7 days after operation;
• Two consecutive test points missing or three plasma samples missing in total before a positive ctDNA time point
• Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
• Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;
• Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;
• Patients with the following serious or uncontrollable diseases: severe heart disease, the condition is still unstable after treatment, including myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment; definite neuropathy or psychosis, including dementia or seizures; severe or uncontrolled infection; active disseminated intravascular coagulation and obvious bleeding tendency;
• Significant impairment of important organ function;
• Other conditions in which the investigator believes that the patient should not participate in this trial.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ctDNA dynamic monitoring + routine postoperative follow-up	ctDNA dynamic monitoring	ctDNA is detected before operation, before chemotherapy, and then every three months for 2 years, 10 times in total. At the same time, routine postoperative follow-up is given. To be pointed out, after the completion of the adjuvant chemotherapy, if the ctDNA test indicates positive, patients will immediately perform chest, abdominal and pelvic CT and other imaging tests to determine whether there is recurrence /metastasis. If it is not confirmed, repeat the imaging review every two months, and continue to perform ctDNA test every three months. If the following ctDNA test is negative for two consecutive times, the above imaging reexamination will return to the routine follow-up frequency. In addition, during the follow-up, the following situations may occur: the imaging examination has found recurrence/metastasis, but the ctDNA test is still negative. At this time, the patient will be informed and treated in time of the recurrence/metastasis.

Primary Outcome Measures

Name	Time	Method
Accuracy of postoperative ctDNA in monitoring recurrence and metastasis	Up to 60 months.	True positive+True negative/sample size
Secondary resection rate	Up to 60 months.	The rate of R0 resection for recurrence or metastasis after surgery of the primary
Specificity of postoperative ctDNA in monitoring recurrence and metastasis	Up to 60 months.	Number of patients with ctDNA negative and no recurrence and metastasis confirmed by imaging / number of patients with no recurrence and metastasis confirmed by imaging
Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis	Up to 60 months.	Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis

Secondary Outcome Measures

Name	Time	Method
ctDNA-disease free survival (DFS)	Under ctDNA monitoring, from date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.	Disease free survival time under ctDNA monitoring
overall survival (OS)	From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.	Overall survival of included patients
ctDNA clearance rate	Up to 60 months.	The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy
CT-DFS	Under imaging monitoring, from date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.	Disease free survival time under imaging monitoring
△DFS	Up to 60 months.	The difference between ctDNA-DFS and CT-DFS

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China