Back to resultsEvaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study
Primary Purpose
Stage III Colorectal Cancer, Circulating Tumor DNA
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
ctDNA dynamic monitoring
Sponsored by
About this trial
This is an interventional diagnostic trial for Stage III Colorectal Cancer focused on measuring Surveillance strategy, Stage III colorectal cancer, Circulating tumor DNA
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.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
ctDNA dynamic monitoring + routine postoperative follow-up
routine postoperative follow-up
Arm Description
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.
Only routine postoperative follow-up is given as follows: Physical examination and CEA were performed every 3-6 months for the first 2 years, every 6 months within the third to fifth year, and then annually. Chest/abdominal/pelvis computed tomography was performed annually for up to 5 years, and colonoscopy was performed for proper patients the first year after treatment and repeated in the third year if no advanced adenoma was found and then every 5 years.
Outcomes
Primary Outcome Measures
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
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
Accuracy of postoperative ctDNA in monitoring recurrence and metastasis
True positive+True negative/sample size
Secondary resection rate
The rate of R0 resection for recurrence or metastasis after surgery of the primary
Secondary Outcome Measures
ctDNA-disease free survival (DFS)
Disease free survival time under ctDNA monitoring
CT-DFS
Disease free survival time under imaging monitoring
△DFS
The difference between ctDNA-DFS and CT-DFS
overall survival (OS)
Overall survival of included patients
ctDNA clearance rate
The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05161585
Brief Title
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
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Colorectal Cancer, Circulating Tumor DNA
Keywords
Surveillance strategy, Stage III colorectal cancer, Circulating tumor DNA
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Postoperative adjuvant therapy (chemotherapy and radiotherapy) and specific implementation scheme shall be determined by the clinical physician blinded to ctDNA status and randomized group. Other parts are open-label.
Allocation
Randomized
Enrollment
316 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ctDNA dynamic monitoring + routine postoperative follow-up
Arm Type
Experimental
Arm Description
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.
Arm Title
routine postoperative follow-up
Arm Type
No Intervention
Arm Description
Only routine postoperative follow-up is given as follows: Physical examination and CEA were performed every 3-6 months for the first 2 years, every 6 months within the third to fifth year, and then annually. Chest/abdominal/pelvis computed tomography was performed annually for up to 5 years, and colonoscopy was performed for proper patients the first year after treatment and repeated in the third year if no advanced adenoma was found and then every 5 years.
Intervention Type
Diagnostic Test
Intervention Name(s)
ctDNA dynamic monitoring
Intervention Description
ctDNA is detected before operation, before chemotherapy, and then every three months for 2 years, 10 times in total.
Primary Outcome Measure Information:
Title
Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis
Description
Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis
Time Frame
Up to 60 months.
Title
Specificity of postoperative ctDNA in monitoring recurrence and metastasis
Description
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
Time Frame
Up to 60 months.
Title
Accuracy of postoperative ctDNA in monitoring recurrence and metastasis
Description
True positive+True negative/sample size
Time Frame
Up to 60 months.
Title
Secondary resection rate
Description
The rate of R0 resection for recurrence or metastasis after surgery of the primary
Time Frame
Up to 60 months.
Secondary Outcome Measure Information:
Title
ctDNA-disease free survival (DFS)
Description
Disease free survival time under ctDNA monitoring
Time Frame
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.
Title
CT-DFS
Description
Disease free survival time under imaging monitoring
Time Frame
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.
Title
△DFS
Description
The difference between ctDNA-DFS and CT-DFS
Time Frame
Up to 60 months.
Title
overall survival (OS)
Description
Overall survival of included patients
Time Frame
From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.
Title
ctDNA clearance rate
Description
The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy
Time Frame
Up to 60 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Junjie Peng, MD, PhD
Phone
86-18017317122
Email
pengjj67@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yaqi Li
Phone
86-15902194450
Email
yaqi702@hotmail.com
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junjie Peng, MD, PhD
Phone
86-18017317122
Email
pengjj67@hotmail.com
First Name & Middle Initial & Last Name & Degree
Yaqi Li, MD, PhD
Phone
86-15902194450
Email
yaqili702@hotmail.com
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study
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