Clinical trial NCT05161585: Evaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study
Official title: Evaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Stage III Colorectal Cancer
Circulating Tumor DNA
Keywords: Surveillance strategy
Stage III colorectal cancer
Circulating tumor DNA
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-12-17
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis
timeFrame: Up to 60 months.
measure: Specificity of postoperative ctDNA in monitoring recurrence and metastasis
timeFrame: Up to 60 months.
measure: Accuracy of postoperative ctDNA in monitoring recurrence and metastasis
timeFrame: Up to 60 months.
measure: Secondary resection rate
timeFrame: Up to 60 months.
Secondary outcomes:
measure: ctDNA-disease free survival (DFS)
timeFrame: 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.
measure: CT-DFS
timeFrame: 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.
measure: △DFS
timeFrame: Up to 60 months.
measure: overall survival (OS)
timeFrame: From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.
measure: ctDNA clearance rate
timeFrame: Up to 60 months.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: