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

Circulating Tumor DNA Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05161585
• Other study ID #: ctDNA- phaseIIICRC
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: September 2024

Study information

• Verified date: December 2021
• Source: Fudan University
• Contact: Junjie Peng, MD, PhD
• Phone: 86-18017317122
• Email: pengjj67[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 316
• Est. completion date: September 2024
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Circulating Tumor DNA
• Colorectal Neoplasms
• Stage III Colorectal Cancer

Intervention

Diagnostic Test:
• ctDNA dynamic monitoring
ctDNA is detected before operation, before chemotherapy, and then every three months for 2 years, 10 times in total.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis	Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis	Up to 60 months.
Primary	Specificity of postoperative ctDNA in monitoring recurrence and metastasis	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	Up to 60 months.
Primary	Accuracy of postoperative ctDNA in monitoring recurrence and metastasis	True positive+True negative/sample size	Up to 60 months.
Primary	Secondary resection rate	The rate of R0 resection for recurrence or metastasis after surgery of the primary	Up to 60 months.
Secondary	ctDNA-disease free survival (DFS)	Disease free survival time under ctDNA monitoring	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.
Secondary	CT-DFS	Disease free survival time under imaging monitoring	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.
Secondary	?DFS	The difference between ctDNA-DFS and CT-DFS	Up to 60 months.
Secondary	overall survival (OS)	Overall survival of included patients	From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.
Secondary	ctDNA clearance rate	The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy	Up to 60 months.